- 1. CHAPTER 10: IMMUNITY EDWARD JENNER The Influenza Epidemic of
1918 1919 killed 22 million people in 18 months
2.
- Describe Definition: Immunity
- Describe Antibodies: Structure and Classes
- Explain and Compare Humoral and Cell Mediated immunity
- Describe Lymphoid Organs Roles in Immunity
- Describe Antigen-antibody Reactions
3. INTRODUCTION
- An animal must defend itself against unwelcome intruders the
many potentially dangerous viruses, bacteria and other pathogens it
encounters in the air, in food and in water
- It must also deal with abnormal body cells, in some cases , may
develop into cancer
4.
- Three cooperative lines of defense have evolved to counter this
threats
- Two of these are non-specific that is they do not distinguish
one infectious agent from another
5. First line barriers to infection
- Intact skin is a barrier that cannot normally be penetrated by
bacteria or viruses although even minute abrasions may allow their
passage
- Likewise, the mucous membranes that line the digestive,
respiratory, and genitourinary tracts bar the entry of potentially
harmful microbes
6.
- In humans, secretions from sebaceous and sweat glands give the
skin a pH ranging from 3 to 5, which is acidic enough to prevent
colonization by many microbes
- Microbial colonization is also inhibited by the washing action
of saliva, tears and mucous secretion
- All these secretions contain antimicrobial proteins
- One of these, the enzyme lysozyme, digests the cell walls of
many bacteria, destroying them
7. Second line barriers
- Microbes that penetrate the first line defense face the second
line defense, which depends mainly onphagocytosis , the ingestion
of invading organisms by certain types of white cells.
- Phagocyte function is intimately associated with an effective
inflammatory response and also with certain antimicrobial
proteins.
8. 9. Neutrophils
- Constitute about 60 - 70% of all leukocytes
- Cells damaged by invading microbes release chemical signals
that attract neutrophils from the blood
- The neutrophils enter the infected tissue, engulfing them and
destroying microbes there
- Neutrophils tend to self-destruct as they destroy foreign
invaders, and their average life span is only a few days
10. Monocytes
- Provide an even more effective phagoytic defense
- After a few hours in the blood, they migrate into tissues and
develop into macrophages : large, long-lived phagocytes
11. These cells extend long pseudopodia that can attach to
polysaccharides on a microbes surface, engulfing the microbes by
phagocytosis, and fusing the resulting vacuole with a lysosome 12.
Eosinophils
- About 1.5% of all leukocytes
- Contribute to defense against large parasitic invaders, such as
the blood fluke,Schistosoma mansoni
- Eosinophils position themselves against the external wall of a
parasite and discharge destructive enzymes from the cytoplasmic
granules
13.
- The blood fluke Schistosomainfects 200 million people, leading
to body pains, anemia, and dysentery.
14. THE INFLAMMATORY RESPONSE
- Damage to tissue by a physical injury or by the entry of a
microorganisms triggers a localized inflammatory response
- One of the chemical signals is histamine
- Histamine is released by circulating leukocytes called
basophils and by mast cells in connective tissues
15.
- Cells of a tissue injured by physical damage or bacteria
release chemical signals such as histamine and prostaglandin
- In response to the signals, nearby capillaries dilate and
became more permeable. Fluid and clotting elements move from the
blood to the site and clotting begins.
- Chemokines and other chemotactic factors released by various
kinds of cells attract phagocytic cells from the blood
- When the phagocytic cells arrive at the site of injury, they
consume pathogens and cell debris, and the tissue heals
16. THIRD LINE OF DEFENSE ~ SPECIFIC IMMUNITY
- While microorganisms are under assault by phagocytic cells, the
inflammatory response and antimicrobial proteins, they inevitably
encounter lymphocytes, the key cells of the immune system
- Lymphocytes generate efficient and selective immune responses
that work throughout the body to eliminate particular invaders
17. Lymphocytes
- The vertebrate body is populated by two main types of
lymphocytes :
- ~Both types of lymphocytes circulate throughout the blood and
lymph and are concentrated in the spleen, lymph nodes and other
lymphatic tissue.
18.
- Lymphocytes, like all blood cells, originate from pluripotent
stem cells in the bone marrow or liver of a developing fetus.
19.
- Early lymphocytes are all alike, but they later develop into T
cells or B cells, depending on where they continue their
maturation.
- Lymphocytes that migratefrom the bone marrow tothymus develop
into T cells.
- Lymphocytes that remainin the bone marrow andcontinue their
maturationthere become B cells.
20. T CELLS
- There are four main types of T cells:
- Cytotoxic T cells (T C )(killer cells) ~ destroy the antigen
directly by attaching to them and releasing the chemical perforin
to kill them
- Helper T cells (T H )~ attract and stimulate macrophages and
promote the activity of other T- and B- cells to increase antibody
production
21.
- Memory T-cells~ have no action but multiply very fast if a
second invasion of the antigen occurs, producing an even bigger
clone of T-lymphocytes and resulting in rapid destruction of
antigen
- Suppressor T-cells~ slow down the vigorous response of the T
Cand T Hcells, so slowing down and the stopping the immune
response
22. B CELLS
- There are three different types of B cells :
- Plasma B cells~ secrete antibodies into the circulation
- Memory B cells~ livefor a long time in the blood. They do not
produce antibodies but are programmed to remember a specific
antigen and respond very rapidly to any subsequent infection
- Dividing B cells~ produce more B lymphocyte cells
23. 24.
- Because lymphocytes recognize and respond to particular
microbes and foreign molecules, they are said to
displayspecificity
- B cells and T cells specialize in different types of antigens,
and they carry out different, but complementary, defensive
actions
25. Antigen (Immunogen)
- Any substances capable of stimulating an immune response,
usually a protein or a large carbohydrate that is foreign to the
body
26. Characteristics of antigens
- Foreign to host ~ chemical groupings (markers) must be
different from those on host cells (receptors) called antigenic
determinants or epitopes
- Possesses two or more antigenic determinants ~ epitopes (2
bivalent, many multivalents)
- May be soluble, particular, cellular
27. A single antigen such as a bacterial surface protein usually
has several effective epitopes, each capable of inducing the
production of specific antibody 28.
- a. Soluble toxins, enzymes, venoms, plant extracts,
medications, foreign serums (proteins)
- b. Particulate ~ cell structures (cell walls, flagella,
capsules, pili), viruses, mold spores, pollens, house dusts
- c. Cellular ~ microorganism, viral infected host cells, foreign
tissue cells, neoplastic cells, altered host cells
29. 30. 11.1.2 ANTIBODY
- One way that an antigen elicits an immune response is by
activating B cells to secrete proteins called antibodies
- Each antigen has a particular molecular shape and stimulates
certain B cells to secrete antibodies that interact specifically
for it.
31.
- Antibodies are glycoproteins which belong to a special group of
blood proteins known as immunoglobulin
- The basic structure of an antibody consists of two pairs of
polypeptide chains
- Two of the chains are long and are referred to asheavy (H)
chains
- The other two shorter chains are referred to aslight (L)
chains
- The chains are held together by disulphide (S-S) bridges to
form the Y-shaped molecule
32. 33. 34.
- Each antibody molecule has two identicalantigen binding
sites
- These are different for each kind of antibody, which allows the
antibody to recognize and attach specifically to a particular
antigen
- The antigen attachment site is known asvariableregion and
specific to each antigen
- The rest of each polypeptide chain is termed
theconstantregion.
35.
36. 37. 38. 10.1.4 Humoral Response(Antibody-Mediated
Immunity)
- B cells responds to antigens by producing antibodies
- Antibodies are secreted into the blood and other body fluids
and thus providehumoral immunity
39. 10.1.5 Cell-mediated Response (Cell-mediated Immunity)
- T cells do not secrete antibodies but instead directly attack
the cells that carry the specific antigens
- These cells are described as producingcell-mediated
immunity
40. 10.1.6 Lymphatic System
- A central location for the collection and distribution of the
cells of the immune system
- Consists of a network of lymphatic capillaries, ducts, nodes
and lymphatic organs
41. 42.
- The fixed macrophages in the spleen, lymph nodes and other
lymphatic tissues are particularly well located to contact
infectious agent
- Interstitial fluid, perhaps containing pathogen, is taken up by
lymphatic capillaries, and flows as lymph, eventually returning to
the blood circulatory system
43.
- Along the way, lymph must pass through numerous lymph nodes,
where any pathogens present must encounter macrophages and
lymphocytes
- Microorganisms, microbial fragments and foreign molecules that
enter the blood encounter macrophages when they become trapped in
the netlike architecture of the spleen
44. Structure of the lymph node 45. Structure of the spleen 46.
The reaction between antibody and antigen
- The antibody becomes attached to the antigen at the antigen
binding site like a key in a lock
- This causes the antibody to change from a T shape to a Y
shape
- This exposes part of the antibody to substances in the plasma
that are together known as complement
47. 48. 49. 50.
- It is the combined effect of antibody and complement that
determines the action of antibody
- The binding of antibodies to antigens to form antigen-antibody
complexes is the basis of several antigen disposal mechanisms
51. 10.1.7Antigen-antibody Interaction
52. i. Neutralization
- The antibody binds to and blocks the activity of the
antigen
- E.g.: Antibodiesneutralizea virus by attaching to molecules
that the virus uses to infect its host cell.
53.
- Similarly, antibodies may bind to the surface of a pathogenic
bacterium
- These microbes, now coated by antibodies, are readily
eliminated by phagocytosis
- In a process calledopsonization (coating) , the bound
antibodies enhance macrophage to, and thus phagocytosis of, the
microbes
54. 55. ii. Agglutination
- Antibody-mediated agglutination (clumping) of bacteria or
viruses effectively neutralizes and opsonizes the microbes
- Agglutination is possible because each antibody has at least
two antigen-binding sites (IgG)
- IgM can link together five or more viruses or bacteria
56.
- These large complexes are readily phagocytosed by
macrophages
57. iii. Precipitation
- In precipitation, the cross-linking of soluble antigen
molecules molecules dissolved in body fluids forms immobile
precipitates that are disposed of by phagocytosis
58. 59. iv. Complement Fixation
- During complement fixation, the antigen-antibody system
activates the complement system, a complex of 20 different serum
proteins
- In an infection, the first in a series of complement proteins
is activated, triggering a cascade of activation steps, each
component activating the next in series
60.
- Completion results in the lysis of many types of viruses and
pathogenic cells
- Lysis can be achieved in two ways:
61. 62. i. The Classical Pathway
- Is triggered by antibodies bound to antigen and is therefore
important to immune response
- Begins when IgM or IgG antibodies bind to a pathogen
63.
- The first complement component links two bound antibodies and
is activated, initiating a cascade
- Ultimately, complement proteins generate a membrane attack
complex (MAC), which forms a pore in the bacterial membrane,
resulting in cell lysis.
64.
- Antibody molecules attach to antigens on pathogens plasma
membrane
- Complement proteins link two antibody molecules
- Activated complement proteins attach to pathogens membrane in
step-by step sequence, forming a membrane attack complex (MAC)
- MAC pores in the membrane causes cell lysis.
65. ii. The Alternative Pathway
- Is triggered by substances that are naturally present on many
bacteria, yeast, viruses and protozoan parasites
- It does not involved antibodies and thus is an important non
specific defense.
66.
- In both the classical and alternative pathways, many activated
complement proteins contribute to inflammation.
- Some triggers the release of histamine by binding the basophils
and mast cells
- Several active complement proteins also attract phagocytes to
the site.
67.
- One activated complement protein coats bacterial surfaces and
stimulates phagocytosis, like antibody
- During immune adherence, microbes coated with antibodies and
complement adhere to blood vessels walls, making the pathogens
easier prey for phagocytic cells circulating in the blood
68. Summary of Antibody-antigen Interaction 69. 10.2 Development
of Immunity 70.
- Describe and explain primary and secondary immune responses to
antigen.
- Explain the concept of self and non-self recognition and its
application in organ transplant, grafting and blood
transfusion.
71.
- Antigens interact with specific lymphocytes, inducing immune
responses and immunological memory
72.
- Although it encounters a large repertoire of B and T cells, a
microorganism interacts only with lymphocytes bearing receptors
specific for its various antigenicmolecules
- The selection of a lymphocytes by one of the microbes antigens
activate the lymphocyte, stimulating it to divide and differentiate
and eventually, producing two clones of cells
CLONAL SELECTION 73.
- One clone consists of a large number ofeffector cells ,
short-lived cells that combat the same antigen
- Effector cellsare populations of cells resulting from divisions
of lymphocytes that were activated by the binding of antigens to
their antigen receptors
- The other clone consists ofmemory cellsbearing the receptors
for the same antigen
74. Antigen molecules bind to the antigen receptors of only one
of the six B cells shown The selected B cell proliferates to give
rise to a clone of identical cells bearing receptors for the
selecting antigen Some proliferating cells develop into long-lived
memory cells that can respond rapidly upon subsequent exposure to
the same antigen Some proliferating cells develop into short-lived
plasma cells that secrete antibody specific for the antigen 75.
- The selective proliferation and differentiation of lymphocytes
that occur the first time the body is exposed to an antigen is
theprimary immune response
- About 10 17 days lag period between initial exposure and
production of effector cells
PRIMARY IMMUNE RESPONSE 76.
- During this period, selected B cells and T cells generate
antibody-producing effector B cells, called plasma cells, and
effector T cells respectively
- While this response is developing, a stricken individual may
become ill, but symptoms of the illness diminish and disappear as
antibodies and effector T cells clear the antigen from the
body
77.
- A second exposure to the same antigen at some later time
elicits the secondary immune response
- This response is faster (only 2 to 7 days), of greater
magnitude and more prolonged
- The antibodies produced in the secondary response tend to have
greater affinity for the antigen than those secreted in the primary
response
SECONDARY IMMUNE RESPONSE 78. 79. 80.
- The immune systems capacity to generate secondary immune
response is calledimmunological memory , based not only on effector
cells, but also clones of long-lived T and B memory cells
IMMUNOLOGICAL MEMORY 81.
- Memory cells are not active during primary response and survive
in the system for long periods.
- When the same antigen that caused a primary immune response
again enters the body, the memory cells are activated and rapidly
proliferate to form a new clone of effector cells and memory
cells
- These new clones of effector and memory cells are the secondary
immune response
82. 83. The Development of Active Immunity
- 1. Immunity to smallpox in Jenners patients occurred because
their inoculation with cowpox stimulated the development of
lymphocyte clones with receptors that could bind not only to cowpox
but also to smallpox antigens.
84.
- 2. As a result of clonal selection, a second exposure, this
time to smallpox, stimulates the immune system to produce large
amounts of the antibody more rapidly than before.
85. 10.2.1 Self and Non-self Recognition
- Lymphocytes do not react to most self antigens, but T cells do
have a crucial interaction with one important group of native
molecules
- These are a collection of cell surface glycoproteins encoded by
a family of genes called themajor histocompatibility complex (MHC)
or specifically in humans, human leukocyte antigens (HLA)
86.
- Two main classes of MHC molecules mark body cells as self
- Class I MHC molecules are found on almost all nucleated cells
that is on almost every cells
- ~ the interaction between the antigen-presenting infected cell
is greatly enhanced by a T cell surface protein called CD8
87.
- ii.Class II MHCmolecules are restricted to few specialized cell
types, including macrophages, B cells, activated T cells and those
inside the thymus
- ~ The interaction between antigen-presenting cell and a T Hcell
is greatly enhanced by CD4
88. MHC
- It is unlikely that any two people, except identical twins,
will have the same set of MHC molecules
- The MHC provides a biochemical fingerprint virtually unique to
each individual
- MHC molecules vary from person to person because of their
central role in the immune system
89.
- There are two main types of T cells, and responds to one class
of MHC molecules
- Cytotoxic T cells (T C ) have antigen receptors that bind to
protein fragments displayed by the bodys class I MHC molecules
- ~ Tc responds by killing the infected cells
90.
- A fragment of foreign protein (antigen) inside the cell
associates with an MHC molecule and transported to the cell
surface.
- The combination of MHC molecule and antigen is recognized by a
T cell, alerting it to the infection.
(CD8 protein) 91.
- ii. Helper T cells (T H ) have receptors that bind to peptides
displayed by the bodys class II MHC molecules
- ~ Macrophages and B cells (antigen - presenting cells, APCs),
ingest bacteria and viruses and then destroy them
92.
- A fragment of foreign protein (antigen) inside the cell
associates with an MHC molecule and transported to the cell
surface.
- The combination of MHC molecule and antigen is recognized by a
T cell, alerting it to the infection.
(CD4 protein) 93. Fig. 57.9 94. IMMUNE RESPONSES 95. The immune
system can mount two types of responses depending on the antigen
which stimulates the system i. Humoral response ii. Cell-mediated
response
- Humoral immunity: involves B cell activation and results from
the production of antibodies that circulate in the blood plasma and
lymph
- Circulating antibodies defend mainly against free bacteria,
toxins and viruses in the body fluid
96.
- Cell-mediated immunity: T lymphocytes attack viruses and
bacteria within infected cells and defend against fungi, protozoa
and parasitic worms
- They also attack non-self cancer and transplant cells
97.
- The humoral and cell-mediated immune responses are linked by
signalling interactions, especially via the T cells
98. 99.
- 1. Helper T lymphocytes function in both humoral and
cell-mediated immunity
Development of Cellular Immunity 100.
- Both types of immune responses are initiated by interactions
between antigen-presenting cells (APCs) and T Hcells
- The APCs, including macrophages and some B cells, tell the
immune system, via T Hcells, that a foreign antigen is in the
body
- At the heart of the interactions between APCs and T Hcells are
class II MHC molecules produced by the APCs, which bind to foreign
antigens
101. 102.
- An APC engulfs a bacterium and transport a fragment of it to
the cell surface via a class II MHC molecule
- A specific T Hcell is activated by binding to the MHC-antigen
complex. The CD4 protein of the T Hcells enhances the activation,
as does interleukin-1 (IL-1) secreted by the APC
- The activated T Hcell proliferates, giving rise to a clone of
identical clones (not shown), all with receptors keyed to the same
MHC-antigen combination. These cells secrete cytokines (e.g. :
Interleukin-2)
- The cytokines further stimulate the T Hcells and also help
activates B cells and T Ccells
103.
- Activated TH cells that bind to a class II MHC-antigen complex
on an APC are induced to differentiate into either of two clones of
cells :
- i.Activated T Hcells~ secrete cytokines, factors that stimulate
other lymphocytes (e.g. : IL-2 stimulates differentiation of B
cells into antibody-secreting plasma cells and induces T Ccells to
become active killers)
104.
- ii.Memory T Hcells~ IL-1 secreted from APCs, promotes
activation of the T Hcells and the subsequent secretion of IL-2
from the activated T Hcell.
- ~ T Hcells themselves are regulated by cytokines
105.
- 2. In the cell-mediated response, cytotoxic T cells defend
against intracellular pathogens
106.
- Antigen-activated T Ccells, kill cancers cells and cells
infected by viruses and other intracellular pathogens
- This is mediated through class 1 MHC molecules
- All nucleated cells continuously produce class 1 MHC molecules,
which capture a small fragment of one of the other proteins
synthesized by that cell and carries it to the surface
107.
- An infected cell (or cancer cell) displays as an antigen
fragment on its surface using a class I MHC molecule. A specific T
Ccell is activated by binding to the MHC-antigen complex. The CD8
protein of the T Ccell enhances the activation, along with IL-2
from T Hcells (not shown)
- The activated T Ccell discharges perforin molecules, which
create pores in the membrane of the infected cell.
- Water and ions flow into the infected cell, and the cell
lyses.
108. Cytotoxic T cell 109.
- Destruction of the host cell not only removes the site where
pathogens can reproduce, but also exposes the pathogens to
circulating antibodies from humoral response.
- T Ccontinue to live after destroying the infected cell and may
kill many others displaying the same antigen-class I MHC
marker
110.
- T Calso function to destroy cancer cells
- Cancer cells possess distinctive markers not found on normal
cells, known astumor antigen
- T cells recognize these markers as non-self and attach and lyse
the cancer cells
- Certain types of cancers and viruses have diminish the amounts
of class I MHC proteins on affected cells, thereby reducing the
ability of T Cto recognize and destroy them
111. 112. Development of Humoral Immunity
- 3. In the humoral response, B cells make antibodies against
extracellular pathogens
113.
- The humoral response occurs when an antigen binds to B cell
receptors that are specific for the antigen epitopes
- The B cells differentiate into a clone of plasma cells which
begin to secrete antibodies that are most effective against
pathogens circulating in the blood and lymph
- Memory cells are also produced and form the basis for secondary
immune responses
114.
- A macrophage ingests a pathogen
- Class II MHC proteins within the cell bind to fragments of the
pathogen and transport them to the cell surface
- A T Hcell with a receptor specific for the presented antigen
contacts the macrophage and is induced to proliferate and secrete
cytokines
- The activated T Hcell binds with a B cell that has previously
taken up antigen. As an APC, the B cells class II MHC molecules
present fragments of the antigen. Cytokines help activate the B
cell.
- The B cell proliferates and differentiates into memory cells
and plasma cells that secrete antibody molecules specific for the
bacterium.
115.
- When activated a B cell gives rise to a clone of plasma
cells.
- Each of these effector cells secretes up to 2000 antibodies per
second into body fluids for its 4 5 day lifespan
- The specific antibodies help eliminate the foreign invader from
the body
116. 117. The immune systems capacity to distinguish self from
nonself limits blood transfusion and tissue transplantation
118.
- In addition to attacking pathogens, the immune system will also
attack cells from other individuals.
-
- For example, a skin graft from one person to a nonidentical
individual will look healthy for a day or two, but it will then be
destroyed by immune responses.
-
- Interestingly, a pregnant woman does not reject the fetus as a
foreign body, as apparently, the structure of the placenta is the
key to this acceptance.
119.
- One source of potential problems with blood transfusions is an
immune reaction from individuals with incompatible blood
types.
-
- In theABO blood groups , an individual with type A blood has A
antigens on the surface of red blood cells.
-
-
- This is not recognized as an antigen by the owner, but it can
be identified as foreign if placed in the body of another
individual.
-
- B antigens are found on type B red blood cells.
-
- Both A and B antigens are found on type AB red blood
cells.
-
- Neither antigen is found on type O red blood cells.
120.
- A person with type A blood already has antibodies to the B
antigen, even if the person has never been exposed to type B
blood.
-
- These antibodies arise in response to bacteria (normal flora)
that have epitopes very similar to blood group antigens.
-
- Thus, an individual with type A blood does make antibodies to
A-like bacterial epitopes - these are considered self - but that
person does make antibodies to B-like bacterial epitopes.
-
- If a person with type A blood receives a transfusion of type B
blood, the preexisting anti-B antibodies will induce an immediate
and devastating transfusion reaction.
121. 122.
- However, another blood group antigen, theRh factor , can cause
mother-fetus problems because antibodies produced to it are
IgG.
-
- This situation arises when a mother that is Rh-negative (lacks
the Rh factor) has a fetus that is Rh-positive, having inherited
the factor from the father.
-
- If small amounts of fetal blood cross the placenta as may
happen late in pregnancy or during delivery, the mother mounts a
T-dependent humoral response against the Rh factor.
-
- The danger occurs in subsequent Rh-positive pregnancies, when
the mothers Rh-specific memory B cells produce IgG antibodies that
can cross the placenta and destroy the red blood cells of the
fetus.
123.
- To prevent this, the mother is injected with anti-Rh antibodies
after delivering her first Rh positive baby.
-
- She is, in effect, passively immunized (artificially) to
eliminate the Rh antigen before her own immune system responds and
generates immunological memory against the Rh factor, endangering
her future Rh-positive babies.
124. 10.3 Immune Disorder: SLE and AIDS 125.
- Briefly explain SLE, AIDS
- Explain the mechanism of action of HIV Infection and Symptoms
of AIDS.
- List the possible causes and prevention of HIV Infection.
126.
- Malfunctions of the immune system can produce effects ranging
from the minor inconvenience of some allergies to the serious and
often fatal consequences of certain autoimmune and immunodeficiency
diseases.
127.
- Allergiesare hypersensitive (exaggerated) responses to certain
environmental antigens, called allergens.
-
- One hypothesis to explain the origin of allergies is that they
are evolutionary remnants of the immune systems response to
parasitic worms.
-
- The humoral mechanism that combats worms is similar to the
allergic response that causes such disorders ashay feverandallergic
asthma.
128.
- The most common allergies involve antibodies of the IgE
class.
-
- Hay fever, for example, occurs when plasma cells secrete IgE
specific for pollen allergens.
-
- Some IgE antibodies attach by their tails to mast cells present
in connective tissue, without binding to the pollen.
-
- Later, when pollen grains enter the body, they attach to the
antigen-binding sites of mast cell-associated IgE, cross-linking
adjacent antibody molecules.
129.
- This event triggers the mast cell todegranulate- that is, to
release histamines and other inflammatory agents from vesicles
called granules.
130.
- High levels of histamines cause dilation and increased
permeability of small blood vessels.
-
- These inflammatory events lead to typical allergy symptoms:
sneezing, runny nose, tearing eyes, and smooth muscle contractions
that can result in breathing difficulty.
-
- Antihistamines diminish allergy symptoms by blocking receptors
for histamine.
131.
- Sometimes, an acute allergic response can result inanaphylactic
shock , a life threatening reaction to injected or ingested
allergens.
-
- Anaphylactic shock results when widespread mast cell
degranulation triggers abrupt dilation of peripheral blood vessels,
causing a sudden drop in blood pressure.
-
-
- Death may occur within minutes.
-
- Triggers of anaphylactic shock in susceptible individuals
include bee venom, penicillin, or foods such as peanuts or
fish.
-
- Some hypersensitive individuals carry syringes with
epinephrine, which counteracts this allergic response.
132. Tissue grafts and organ transplantation
- The MHC is responsible for stimulating the rejection of tissue
grafts and organ transplants.
- Because MHC creates a unique protein
- fingerprint for each individual, foreign
- MHC molecules are antigenic, inducing
- immune responses against the donated
133.
- To minimize rejection, attempts are made to match MHC of tissue
donor and recipient as closely as possible.
- In the absence of identical twins,
- siblings usually provide the closest
134.
- In addition to MHC matching, various medicines are necessary to
suppress the immune response to the transplant.
- However, this strategy leaves the
- recipient more susceptible to
- infection and cancer during the
135.
- More selective drugs, which suppress helper T cell activation
without crippling nonspecific defense or T-independent humoral
responses, have greatly improved the success of organ
transplant.
136.
- In bone marrow transplants, it is the graft itself, rather than
the host, that is the source of potential immune rejection.
- Bone marrow transplants are usedto treat leukemia and
othercancers as well as varioushematological diseases.
137.
- Prior marrow transplants, therecipient is typically treated
with
- irradiation to eliminate the
- recipients immune system, leaving
- little chance of graft rejection.
- However, the donated marrow,
- containing lymphocytes, may react
- against the recipient, producing graft
- versus host reaction, unless well
138. AUTOIMMUNE DISEASES The Body Attacks Itself
- Autoimmunity arises when the immune system fails to distinguish
between self and non-self (foreign) cells, and attacks self, or
body tissues.
- Causes generally not known, but may involve genetic, viral and
environmental factors or after recovery from infection.
139. e.g. Autoimmune diseases
- Systemic lupus erythematosus
- Heart damage following rheumatic fever & Type I
diabetes.
140. Rheumatoid Arthritis ofthe Hands Rheumatoid arthritis can
result in severe deformation of the hands, wrists, feet, ankles,
hips, and shoulders. The characteristic swelling, pain, and
restricted movement Rheumatoid arthritis can result in severe
deformation of the hands, wrists, feet, ankles, hips and shoulders.
The characteristic swelling, pain and restricted movement 141.
Multiple sclerosis
-
-
- In this i ll ness the myelin sheath covering the spinal cord is
destroyed, leading to difficulty in walking and other movements.
The damage in multiple sclerosis is not produced by an auto
antibody but by a lymphocyte that reacts directly with the
protective sheath.
142. Myasthenia gravis Myasthenia gravis is a neuromuscular
disease that causes weakness and fatigue, most commonly in the
muscles of the eyes, face, throat and limbs. MG is an acquired
disease, meaning it isn't inherited as a genetic disease.The word
"myasthenia" means muscle weakness. 143. Systemic lupus
erythematosus 144.
- In SLE (lupus), the immune system generates antibodies against
all sorts of self molecules, including histamines
- Lupus is characterized by skin rashes, fever, arthritis and
kidney dysfunction
145. A I D S C QUIRED MMUNO - EFICIENCY YNDROME 146.
INTRODUCTION 147.
- In 1981, increased rates of two rare diseases, Kaposis sarcoma,
a cancer of the skin and blood vessels, and pneumonia caused by the
protozoanPneumocystis carinii , were the first signals to the
medical community of a new threat to humans, later known as
acquiredimmunodeficiency syndrome , orAIDS .
-
- Both conditions were previously known to occur mainly in
severely immunosuppressed individuals.
148.
-
- People with AIDS are susceptible toopportunistic diseases
.
- Opportunistic disease: infection rarely observed in humans with
normal immune response
- Eg : ThePneumocystisprotozoan is an ubiquitous organism, yet it
does not cause pneumonia in a person with a healthy immune
system
- In people with AIDS, opportunistic diseases, neurologic damage
and physiological wasting, lead to death
149.
- In 1983, a retrovirus, now calledhuman immunodeficiency virus(
HIV ) , had been identified as the causative agent of AIDS.
A T cell infected with HIV. The virus (blue) bud continuously
from the surface of the T cell (orange). The cell will die, but
only after it produces many copies of its viral killers 150.
- With the AIDS mortality close to 100%, HIV is the most lethal
pathogen ever encountered.
-
- Molecular studies reveal that the virus probably evolved from
another HIV-like virus in chimpanzees in central Africa and
appeared in humans sometimes between 1915 and 1940.
-
-
- These first rare cases of infection and AIDS went
unrecognized.
151.
- There are two major strains of the virus, HIV-1 and HIV-2.
-
- HIV-1 is the more widely distributed and more virulent.
- Both strains infect cells that bear CD4 molecules, especially
helper T cells and class II MHC-bearing antigen-presenting cells,
but also macrophages, some lymphocytes and some brain cells.
-
- CD4 functions as the major receptor for the virus.
152. Causative Agent
- The viral particle includes:
-
- an envelope with glycoproteinfor binding to receptor molecule
on T Hsurface
- 1. two identical RNA strands as its genome
- 2. two copies of reverse transcriptase.
153. Causative AgentRNA Capsid RNA Reverse transcriptase enzyme
Viralenvelope Glycoprotein 154.
- The entry of the virus requires not only CD4 on the surface of
the susceptible cells but also a second protein molecule,
acoreceptor .
-
- Two of the coreceptors that have been identified normally
function as receptors for chemokines.
-
- Some people who are innately resistant to HIV-1 owe their
resistance to defective chemokine receptors which prevents HIV from
binding and infecting cells.
155. The Causes 156. The Causes mainly because of theexchange of
body fluid:
- Promiscuity (having many transient sexual relationship)
- Through injection drug use
- Prenatal infection or in infancy
157. The Symptoms 158. The SymptomsFlu or mononucleosis
- persistent or recurrent fever
- decreased appetite (rapid
- weight loss) blood/mucus in
159. The SymptomsBehavioral dementia
- (madness) due to the damage
- on nervous system (esp. brain
160. The SymptomsPneumocystis carinii pneumonia (PCP)
- (alveoli filled with fluid)
161. The SymptomsKaposis sarcoma a cancer of the skin andblood
vessels (purplish spot on skin) 162. The mechanism of infection and
HIV replication 163. The Mechanism of infection and the Replication
of HIV
- Glycoprotein on the envelope bind to specific receptors on the
hosts membrane (T Hcell)
- The envelope fuses with the hosts membrane,
- transporting the capsid and viral genome inside
164. 165.
- Reverse transcriptase synthesizes double
- stranded DNA from the viral RNA
The Mechanism of infection and the Replication of HIV 166. 167.
The Mechanism of infection and the Replication of HIV
- The double-stranded DNA is incorporated as
- aprovirusinto the host cell's chromosomal
- DNA, where it may lie dormant for years.
168. The Mechanism of infection and the Replication of HIV
- Theprovirusis transcribed into mRNA and went
- out from the hosts nucleus into its cytoplasm
169. 170. The Mechanism of infection and the Replication of
HIV
- mRNA are translated to viral protein forming :
-
-
-
- reverse transcriptase enzyme
171. The Mechanism of infection and the Replication of HIV
- Protein coats form around viral RNA and reverse
- transcriptase molecules and move towards hosts
172. The Mechanism of infection and the Replication of HIV
- Viruses bud from the host cell, acquiring envelopes
173. 174. 1 2 3 4 5 6 7 8 175. The new HIV particles leaving the
hosts cellMature form Budding particle 176.
- In spite of these challenges, the immune system engages in a
prolonged battle against HIV.
-
- (1) The immune response diminishes the initial viral load, but
HIV continues to replicate in lymphatic tissue.
-
- (2) Viral load gradually rises as HIV is released from
lymphatic tissue and helper T cell levels decrease.
-
- (3) This results in extensive loss of humoral and cell-mediated
immunity.
177. 178. 179. THE STAGES OF HIV INFECTION
- HIV concentration increases rapidly within a 6-month of
infection but is then almost eliminated by the immune
response.
- However, in 1 to 3 years of infection, some of the viruses
survive and slowly increase the number of the viruses.
- In 9 to 10 years of infection, the body almost total loss of
cellular immunity.
- While the T helper cell concentration decreases, AIDS is the
last stage of the process.
180. HIV on a lymphocyte HIV particles 181. Treatment of
AIDS
- No cure for HIV infection is known, although research is
intense in the areas of vaccine production and chemotherapy
- Several drugs have been identified as helpful in delaying
symptoms of AIDS and in some cases in prolonging the life of those
infected with HIV
182.
- The most promising drugs : Azidothymidine (AZT) is an effective
inhibitor of HIV replication
- A major problem observed with many AIDS drugs is that the
compounds are frequently toxic when used on a long term basis
183. The Preventive Measures
- Treat HIV infection as an illness
- Counseling and HIV testing for the patient
- Education for children and adults
- Health care programme providing antiretroviral therapyto extend
life and to reduce HIV transmission rate .
184.
- Antiretroviral therapy for pregnant women
- toreduce prenatal HIV transmission.
- Promote sexual barrier precautions
The Preventive Measures