Definition:

The immune system is a collection of cells and molecules

that provides a defense mechanism to the body, against
antigens that would otherwise prove to be harmful.
Vital for survival; immune deficiencies render the person
easy prey to infections; however, a hyperactive immune
system may cause fatal diseases too

Types of Immunity:
➢ Innate Immunity (Natural/Native Immunity)

➢ Adaptive Immunity (Acquired/Specific Immunity)

Humoral Immunity
Cell-mediated (Cellular) Immunity
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 Mediated by cells and proteins that are
inherently present in the body and immediately
responds to infection; constantly in action
e.g. epithelium of skin, GI tract, and respiratory
tract; phagocytes, natural killer (NK) cells and
proteins of compliment system
Not specific or very powerful; can be overcome
by microbes sometimes

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 Cells of Adaptive immunity more powerful and
specific
Normally silent; becomes active in the presence
of infection
Mediated by:
A. Lymphocytes – both B lymphocytes and T-
lymphocytes
B. Antigen-Presenting Cells (APCs) – capture and
display antigens to lymphocytes
C. Effector Cells – Eliminate the antigens

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They consist of:
➢ T lymphocytes – involved in cell-mediated immunity
▪ mature in the thymus
▪ act against intracellular microbes
▪ can directly kill microbes (by cytotoxic T-
lymphocytes) or activate phagocytes via
mediators called cytokines (from Helper T-
lymphocytes) to kill
➢ B lymphocytes – involved in humoral immunity
▪ mature in bone marrow
▪ produce antibodies;
▪ protect against extracellular microbes
➢ Natural Killer (NK) cells – in innate immunity
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Originate from stem cells in bone marrow and are
differentiated in the Thymus.
Populate in lymph nodes and spleen; account for 60 - 70 %
of lymphocytes in blood.
Cannot directly detect circulating antigens but identify only
the peptides of antigens displayed on other cells
These peptides are bound to protein complexes called
Major Histocompatibility complex (MHC)
MHCs are present on selected cells called Antigen
Presenting Cells (APCs)
MHC genes are inherited from both parents
In addition, subsets of T-cells have other molecules on their
surface, such as CD4 and CD8 that serve as coreceptors for
T-cell activation and bind to MHCs
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 Lymphocyte antigen
receptors
• A: The T-cell receptor (TCR)
complex and other molecules
involved in T-cell activation.
The TCRα and TCRβ chains
recognize antigen (in the form
of peptide–MHC complexes
expressed on antigen-
presenting cells), and the linked
CD3 complex initiates activating
signals. CD4 and CD28 are also
involved in T-cell activation.
(Note that some T cells express
CD8 and not CD4; these
molecules serve analogous
roles.)

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▪ CD4+ T cells account for approximately 60% of circulating T
cells.
➢ CD4+ T-cells are called “Helper T cells”; secrete cytokines
➢ they help B cells to produce antibodies
➢ help macrophages to destroy bacteria
▪ CD8+ T cell account for approximately 40% of circulating T
cells.
➢ CD8+ T-cells are called “Cytotoxic” T-cells
➢ they can directly kill virus –infected or tumor cells

▪ The normal 2:1 ratio of CD4+ to CD8+ cells is dramatically

altered in some disease states. e.g. in AIDS, the ratio is 0.5:1 or
less.
▪ T-cells also have other populations called Regulatory T-cells and
NKT cells
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Consists of a group of proteins referred to as Major
Histocompatibility Complex (MHC). In humans they are
known as HLA antigens (Human Leukocyte Antigens)
Three Types:
1. Class I MHC molecules – present peptides synthesized
within the cell (from viruses) to CD8+ T cells for binding
2. Class II MHC molecules - present peptides synthesized
outside the cell (bacteria) to CD4+ T cells for binding;
found on dendritic cells, macrophages, and B cells
3. Class III MHC molecules – do not display peptides
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Every individual inherits one HLA allele from each parent
Alleles exhibit polymorphism and so several combinations of
molecules exist from the two parents
Each individual has specific alleles and evokes specific immune
responses
Important in organ transplantation, where HLA typing and
matching of the donor and recipient are done to predict tissue
compatibility.
Inheritance of particular alleles can produce protective and
harmful responses. e.g. allergy vs immunity
Many diseases are HLA- linked diseases e.g. ankylosing
spondilitis, autoimmune diseases

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 T cell covered with
receptor molecules
and adhesion proteins

Adhesion proteins help T

cell stick to antigen
presenting cell

Antigen presenting cell (APC) presents

peptides of foreign protein (antigen)
bound to MHC proteins
T-cell receptor recognizes
foreign protein (antigen);
About 100,000 on a T cell

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 Cytotoxic T-Cell Activity

http://highered.mcgraw-
hill.com/sites/9834092339/student_view0/cha
pter51/cytotoxic_t-
cell_activity_against_target_cells.html

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Originate from stem cells in bone marrow; originally
discovered in birds which have a preprocessing organ called
the Bursa of Fabricius
In humans they continue their differentiation within bone
marrow and peripherally, where they cluster in the germinal
centers of lymph nodes and in the follicles of the spleen.
B cells account for 10-20% of circulating blood lymphocytes.
B cells are stimulated by helper T cells that differentiate
them into Plasma cells which secrete antibodies called
immunoglobulins ( Ig)
Each antibody has a unique antigen specificity
B cells recognize many more antigens than T cells

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14
There are 5 classes of immunoglobulins:

IgG
Smallest; Bivalent
Constitute 75% of antibodies in healthy person
IgM
Large share of antibodies during primary response;
found in circulating body fluids
Have 10 binding sites, extremely effective at
protecting body against invaders
IgA - Found in mucosal and body secretions .e.g.
saliva, sweat, tears
IgE - Small percentage, but important in allergic
reactions; also found attached to mast cells
IgD - Found in the tissues that line the belly or chest
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Each B lymphocyte is antibodies
covered with about
100,000 antibodies
Antigen attaches to one
or more antibodies
B lymphocyte is then
activated
Similarly T-Lymphocytes
have surface receptor
proteins (T-cell markers)
that are highly specific
for specific antigens

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They are cells of innate immunity; Are also called large
granular lymphocytes (LGL) because of their distinctive
size, pale cytoplasm, and prominent granulation.

They account for 15% of circulating lymphocytes

They kill infected cells, stressed cells beyond repair and

cells with DNA damage. Neither specific sensitization
nor antibody are involved in this type of cell killing.

They avoid attacking normal host cells

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Have two types of receptors;
Inhibitory – recognize Class I MHCs on healthy cells
Activating – recognize stressed, infected or DNA damaged cells
Normally NKT cells are inhibited

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 Dendritic Cells
Are characterized by dendritic
cytoplasmic processes.
Also stimulate T and B cells
In contrast to macrophages, are
poorly phagocytic.
Two types –
a) Interdigitating DC – Have class
II MHC molecules (HLA) on cell
surface that present antigens to T
cells; present in epithelia of skin
(Langerhans cells), in heart,
lungs, and lymphoid tissues
b) Follicular dendritic cells –
present antigens to B cells in
spleen and lymph nodes 19
Macrophages:
Process and present antigen (along with
HLA class II antigens) to CD4 +T cells.
Macrophages in turn are activated by T-cells
to kill microbes
B-cells:
They present peptides to helper T cells
B-cells in turn receive signals from helper T-
cells that stimulate antibody responses to
antigens
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• http://highered.mheducation.com/sites/9834
092339/student_view0/chapter51/interaction_
of_antigen_presenting_cells_and_t-
helper_cells.html

21
These are cells that perform the ultimate task of
eliminating infections
➢ NK cells – react against infected cells and
“stressed” cells
➢ Plasma cells – in humoral immunity

➢ CD4+ and CD8+ T cells – in cellular immunity

➢ Macrophages – in humoral and cellular immunity;

they phagocytose bacteria
In addition, T lymphocytes secrete cytokines that
activate neutrophils and eosinophils to function as
effector cells in defense against pathogens
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Are soluble proteins secreted by lymphocytes
(lymphokines), monocytes-macrophages
(monokines), and NK cells, as well as other cell types.
Their secretion is transient in response to external
stimuli (microbial products, antigen recognition,
other cytokines)
Act as effector molecules influencing the behavior of
B cells, T cells, NK cells, Monocytes, macrophages,
hematopoetic cells and may other cell types.
They are involved in innate immunity, adaptive
immunity, inflammation and in hematopoiesis
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Consists of about 20 plasma
proteins and their products,
which can be activated by
Classic or Alternate pathway
to form a final product - the
Membrane Attack Complex
(MAC)- that punches holes
in microbes and lyse them

Also participate in
inflammations coating
microbes (Opsonisation) for
phagocytosis

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 Tissues of the Immune System
Consist of:
• Generative lymphoid organs
– T and B lymphocytes mature here and become
competent to respond to antigens, e.g. Thymus and
Bone marrow
• Peripheral lymphoid organs
– Adaptive immune responses to microbes are initiated
here, e.g. lymph nodes, spleen, mucosal and cutaneous
lymphoid tissues
– Antigens, APCs, and lymphocytes are concentrated here
developing the adaptive immune responses
– B cells and T cells are present in the lymphoid follicles
and paracortical areas of peripheral lymphoid organs
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Overall Summary of Immune Response

• http://highered.mcgraw-
hill.com/sites/0072495855/student_view0/chap
ter24/animation__the_immune_response.html

26
 Early Innate Response
Epithelia of skin, GI and Respiratory tracts
serve as principal physical and functional
barriers
If microbes cross this, they are destroyed by
innate immunity mechanisms, by phagocytes
(neutrophils and macrophages) and NK cells, by
phagocytosis, secretion of cytokines, and
proteins of compliment system
In addition, innate response stimulates the
adaptive immunity response
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 Capture and Display of Antigens
Microbes that escape the innate
response are captured by DCs
and transported to lymph nodes
Protein antigens are processed
in APCs to display peptides on
their surfaces and are bound to
MHCs for T-cells to recognize;
antigens are also recognized by
B-cells
In addition, microbes also The innate response also
activate APCs (through innate activates the complement
response) to express co- system which enhances
stimulatory molecules and to proliferation and
secrete cytokines that stimulate differentiation of B cells
T cells proliferation 28
 Normal Immune Response – Contd.
Cell-Mediated Immunity
The T cells are activated in peripheral lymphoid tissues; they proliferate and
differentiate into effector cells and migrate to antigen sites.
Activated CD4+ T cells (Helper cells)
• Secrete cytokines that increase lymphocyte population and
improves their effector function
• Two main subsets exist: TH1 and TH2
• TH1 activate macrophages and stimulate B-cells to produce
antibodies that act as opsonins for phagocytosis
• TH2 cells stimulate IgE producing plasma cells; also stimulate
Eosinophils and epithelial cells to secrete mucus
• also promote inflammatory process (TH17)
Activated CD8+ T cells differentiate into cytotoxic cells (CTLs) that kill
cells with viruses, and bacteria that avoid phagolysosomal killing
within vesicles
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Antibody production Antibody effector functions

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1. Upon activation B lymphocytes differentiate into
plasma cells and secrete antibodies.
✓ Antibodies neutralize microbes and prevent infection
✓ IgG opsonize microbes preparing them for
phagocytosis by neutrophils and macrophages
✓ IgG and IgM activate the complimenting system and
promote phagocytosis
✓ IgG also protects newborn until immune system
becomes mature
✓ IgA neutralizes bacteria in respiratory and GI tracts
✓ IgE, with mast cells and eosinophils, kills parasites

2. B cells also act as APCs and display peptides bound

to Class II MHCs for recognition by Helper T cells
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After elimination of microbe, effector
lymphocytes die by apoptosis; immune system
returns to its basal resting state (homeostasis)
Initial activation of lymphocytes also generate
memory cells that survive for several years after
infection
Memory cells respond faster and more efficiently
against further attack by antigens
Generation of memory cells is the goal of
vaccinations.
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 Adverse reactions caused by immune
mechanisms are termed hypersensitivity
reactions.
1. Type I (anaphylactic)
2. Type II (cytotoxic)
3. Type III (Immune complex)
4. Type IV (cell-mediated)

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 Autoimmunity: Due to reaction against one’s
own antigens; failure of self-tolerance
Aberrant reaction against microbes:
a) Formation of immune complexes that deposit in
tissues and trigger inflammation e.g.
poststreptococcal glomerulonephritis
b) Cross-reaction with host tissue e.g. rheumatic
heart disease
c) Sometimes normal inflammatory reaction to
non-cytopathic microbe occur e.g. viral hepatitis
Unusual reaction to harmless antigens in
environment: e.g. allergies to pollen, dust mite 34
 Type I – Allergic Rhinitis
➢ Occurs within minutes
➢ Interaction of antigen
(allergen) and IgE antibody on
mast cell surface
➢ Leads to secretion of
histamine, proteases,
prostaglandins, leukotrienes
and cytokines
➢ Effects – Immediate - vascular
and smooth muscle reactions;
late-phase reactions – http://highered.mheducation.com/sites/98
prolonged inflammation 34092339/student_view0/chapter51/ige_
mediated__type_1__hypersensitivity.html
➢ Clinical manifestations – Local or systemic,
from mild rhinitis to fatal anaphylaxis 35
Occurs with parenteral administration of
antigen (bee venom, penicillin)
Within minutes – itching, urticaria, erythema
Followed by bronchospasm and increased
mucus secretion; Larngeal edema may cause
airway obstruction; GI tract - vomiting,
abdominal cramps, diarrhea
Systemic vasodilatation → hypotension
(anaphylactic shock), collapse and death
within minutes
https://www.youtube.com/watch?v=TTcL7u05aUU
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The acute laryngeal edema seen here that killed the patient
was due to an anaphylactic reaction to penicillin. Such an
allergy is a form of type I hypersensitivity reaction in which
there is preformed IgE antibody on mast cells that quickly
reacts with an antigen. The mast cells release histamine and
other mediators that lead to the edema. 37
 X

38
Place patient in recumbent position and elevate lower
extremities.
Monitor vital signs frequently (every two to five minutes)
and stay with the patient.
Maintain airway with an oropharyngeal airway device.
Administer oxygen, usually 8 to 10 L per minute; lower
concentrations may be appropriate for patients with
chronic obstructive pulmonary disease.
Treat hypotension with IV fluids or colloid replacement,
If hypotension is present, or bronchospasm persists in an
ambulatory setting, transfer to hospital emergency
department in an ambulance is appropriate
American Family Physician, October 1, 2003

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 Antibody-mediated
(Type II)
▪ Caused by antibodies
(IgG or IgM) that
bind to fixed tissues
or cell surface antigens

▪ Promotes phagocytosis
and lysis of coated
cells or cause functional
derangement in some The bone marrow shown here
tissues, without injury was taken from a patient with
autoimmune hemolytic anemia.
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 Serum Sickness

By immune complexes that occur secondary to

complement activation and circulate in blood or
deposit in vascular beds; release enzymes/toxic subs.
41
T-lymphocytes cause
tissue injury by releasing
cytokines that activate
macrophages and
inflammation, or by
directly killing the host
cells

Two types:
1. Delayed type
hypersensitivity e.g.
tuberculin reaction Poison Ivy
2. Direct cell
cytotoxicity e.g. type 1
diabetes 42
 For a successful graft, donor and recipient must be matched
for ABO blood groups and ideally for as many HLA antigens
as possible.
Types of transplant rejection
1. Hyperacute rejection – antibody-mediated, preformed
antidonor antibodies are present in the circulation of
recipient; rejection within minutes to hours
2. Acute cellular rejection – cell-mediated, within first months;
responds well to ↑’ed immunosuppressive therapy
Acute humoral – antibody-mediated (rejection vasculitis)
3. Chronic rejection (antibody-mediated vascular damage,
fibrosis, and parenchymal damage; months to years)
43
Caused by immune reactions in tissues of host,
with inability to distinguish self from non-self;
there is loss of self-tolerance

Immune responses could be directed at one type

of cell or one organ, or it could be directed at
numerous self-antigens to cause systemic disease
(affects connective tissue and blood vessels)

E.g. autoimmune hemolytic anemia,

Hashimoto’s thyroiditis, autoimmune
hemolytic anemia, and a group of disorders
referred to as connective tissue disorders
44
Self-tolerance means lack of response to self-antigens
Breakdown of tolerance is the basis of autoimmune disease.
Mechanisms of Immunological Tolerance:
Central Tolerance: Immature lymphocytes (T and B) that
can attack self-antigens are selectively deleted in the
central lymphoid organs (thymus and bone marrow);
sometimes B cells undergo rearrangement of genes
(receptor editing)
This is never perfect and some “slippage” occurs
Peripheral tolerance: Aberrant lymphocytes are destroyed in
the peripheral organs by functional inactivation (anergy),
or suppressed by regulatory T cells or die by apoptosis 45
Genetic: Some autoimmune diseases run in families
showing inheritance of susceptible genes; more
common in monozygotic twins than dizygotic; they are
linked with Class II HLA genes
However, the role these genes play is not very clear
Acquired: Microbes (bacteria, mycoplasmas, viruses)
trigger autoimmunity
Immune responses with microbes cross-react with self-
antigens (molecular mimicry) e.g. rheumatic heart
disease (immune response against streptococci cross-
reacts with cardiac antigens)
Breakdown of T-cell anergy by infections
Altered display of antigens
46
Multi-system autoimmune disease with remitting and
relapsing phases
Tolerance has failed in both CD4+ helper T cells and B cells
for specific nuclear self-antigens
Consequently, antibodies are formed against several types
of cells (nuclear and cytoplasmic components) and against
phospholipids
Common in women (80%) of child bearing age.
Characterized by presence of a spectrum of ANAs
(antinuclear antibodies) and by extensive inflammatory cells
involving multiple organ systems, especially the joints, skin,
serous membranes, heart, lungs and kidneys.

47
Fever, malaise,
lymphadenopathy, and
wt. loss,
Joint symptoms,
arthralgia and arthritis.
Skin rashes (butterfly
rash) associated with
photosensitivity
Raynaud’s phenomenon.
Serosal inflammation
(pleuritis, pericarditis)

48
Diffuse interstitial fibrosis
Endocarditis (Libman-Sacks)
Immune complex vasculitis
Glomerular changes varies -
minimal to severe diffuse
proliferative glomerulonephritis
with immune complex deposition,
& thickening of BM
- hematuria, proteiuria, casts
Neurological and psychiatric
manifestations
Eye changes – KCS, keratitis,
cotton-wool patches in retina

49
The young woman has a
malar rash (the so-called
"butterfly" rash because
of the shape across the
cheeks). Such a rash
suggests lupus. Discoid
lupus erythematosus
(DLE) involves mainly
just the skin and is,
therefore, relatively
benign compared to
systemic lupus
erythematosus (SLE). In
either case, sunlight
exposure accentuates
this erythematous rash.
A small number (5 to
10%) of DLE patients go
on to develop SLE
(usually the DLE
patients with a positive
ANA). 50
If an immunofluorescence stain with antibody to
complement or immunoglobulin is performed, then one can
see the brightly fluorescing band along the dermal epidermal
junction that indicates immune complex deposits are present.51
Common, systemic, chronic inflammatory disease affecting
mainly the joints
Caused by autoimmune response to unknown self-antigen
Produces non-suppurative proloferative synovitis that
destroys the cartilage and the under lying bone
Extra-articular sites – skin, heart, blood vessels, muscles,
and lungs
More common in women; peaks in 2nd to 4th decades of life
Principally affects small joints, axial involvement limited to
upper cervical spine
Rheumatoid factor (IgM binding with self-IgG) positive
(+ve) in 80% cases
52
Synovial cell hyperplasia and
proliferation
Inflammatory cells infiltrate
the synovium
Increased vascularity due to
angiogenesis
↑ed osteoclast activity
leading to bone erosion
…. inflammatory cells,
Articular cartilage granulation tissue, fibrous
destruction tissue
Pannus formation - mix of • Pannus eventually fibroses
synovial cells,…… and calcifies causing
ankylosis 53
A. Pannus. B. Low magnification reveals marked synovial
hypertrophy with formation of villi. C. At higher
magnification, dense lymphoid aggregates are seen in the
synovium 54
 With deformity
(Ankylosis)

Rheumatoid Arthritis

With Bony Erosions 55

First described by Henrich SjÖgren in 1933
Autoimmune condition affecting ductal epithelium of
exocrine glands (salivary & lacrimal)
Also B cell hyperactivity seen with ↑ in ANA, RF
Female : male ratio is approximately 10:1
Probable loss of tolerance in the CD4+T cells
Patients present with:
Dry eyes - keratoconjunctivitis sicca
Dry mouth - xerostomia
Bilateral parotid enlargement
Dry vagina
Intense CD4+T cells and plasma cells infiltrates
56
Primary form – isolated disorder; also known as sicca
syndrome
Secondary form - associated with other autoimmune
disease like RA, SLE, Scleroderma, Vasculitis or
Thyroiditis
Also associated with increased risk of B-cell lymphoma

Diagnosis can be confirmed by labial gland biopsy

Treatment is symptomatic
No treatment will reverse the keratoconjunctivitis and
xerostomia

57
58
 Widespread excessive fibrosis over entire body
Initial skin involvement (95%), later GI tract, lungs,
kidneys, heart, skeletal muscles involved.
Incidence – three times more common in women; occurs
between 50-60 years of age
Two types:
➢ Diffuse Scleroderma – early widespread skin and visceral
lesions; rapid progression
➢ Limited Scleroderma – mild skin lesions,
late visceral involvement; benign course
Also called CREST syndrome – Calcinosis,
Raynauds phenomenon, Esophageal
dysmotility, Sclerodactyly, Telangiectasia→
59
Cause unknown
T-cells are activated and release cytokines that activate
mast cells and macrophages
They in turn release fibrogenic cytokines and fibroblast
growth factors
B cell activation also occurs
Two ANAs characteristic of SS:
Anti-Scl 70 (DNA topoisomerase I) – highly specific for
diffuse scleroderma
Anti Centromere Antibody – specific for CREST

60
Extensive collagen in the dermis with Focal or diffuse subcutaneous
Subcutaneous fibrosis creating claw-like calcifications can develop in
deformity with cutaneous ulcerations CREST syndrome 61
X-linked Agammaglobulinemia of
Bruton
Is an X-linked disorder in male infants; presents 6
months after birth
Failure of antibody synthesis, with block in maturation
of pre B cells to B cells.
Absence of immunoglobulins, B cells, and plasma cells
Absent or poorly developed germinal centers in
peripheral lymphoid tissues
Normal T cell mediated responses present
Recurrent bacterial, enteroviral and Giardia infections
occur in these patients

62
 Congenital hypoplasia of thymus
Usually with concomitant hypoplasia
of parathyroid gland, developmental
anomalies in face and aortic arch
Failure of T cell maturation, leading
to lymphopenia; T cells absent in
lymph nodes, spleen, peripheral
blood; B cells unaffected
Patient suffers from recurrent fungal,
viral, and protozoal infections; tetany
from hypoparathyroidism with
hypocalcemia.
• Treatment – transplantation of
thymic tissue 63
 Is caused by human immunodeficiency virus (HIV 1 and 2)
infection, a retrovirus of the lentivirus family
Became a worldwide epidemic since the first clinical
description in 1981.
Since the discovery:
► 22 million have died
► 42 million are living with the disease
► Estimated 5 million infections/year
▪ Characterized by drastic reduction of CD4+T cells,
profound immunosuppression leading to opportunistic
infections, neoplasms, and neurological manifestations

64
Homosexual or Bisexual
men
Intravenous drug abusers
Patients receiving multiple
blood transfusions
Heterosexual partners of
persons on high risk
groups.
Hemophiliacs
Infants of high risk
parents. Structure of HIV-1 Virion

65
HIV virus binds to CD4 molecule on T cells which has
high affinity for the virus; HIV surface protein gp120 must
also bind to other molecules (coreceptors) on cell surface
to facilitate cell entry
Other CD4+ cell types that are targets for HIV infection
include monocytes, macrophages, dendritic cells,
Langerhans’ cells, and microglial cells of the CNS.
The viral surface protein gp41 then changes which allows
it to penetrate the target cell membrane fusing the virus
with the cell.
After internalization of HIV into the cell, the virus
undergoes reverse transcription forming complementary
DNA (cDNA)
66
Molecular basis of HIV entry into host cells. Interactions
with CD4 and a chemokine receptor (“coreceptor”)

67
The cDNA enters the nucleus of dividing T cells and
becomes integrated into the host genome.
After integration, the provirus DNA can proceed in two
ways:
➢ It can remain nontranscribed for months or years – the
infection becomes latent
➢ It can be transcribed to form viral particles that bud
from cell membrane. This leads to cell death.
Loss of CD4+ cells leads to inversion of CD4:CD8 ratio
from 2 to 0.5. Loss of this master cell has ripple effect on
all other cells of the immune system
In addition, the virus is also harbored in monocytes,
macrophages and dendritic cells, and B- cells which also
become defective in function.
68
Begins with acute infection partly controlled by immune
response; memory CD4+T cells in mucosal tissue are the
first to be affected
The huge loss of CD4+ (helper) T cells causes failure in
humoral and cell mediated hypersensitivity reactions
Virus then migrates to lymph nodes and subsequently
passes to CD4+T cells in the lymphoid tissue
Acute infection progresses to chronic phase with severe
viremia in between, accompanied by symptoms of acute
HIV syndrome and host immune responses

69
As a result there is a clinical latency period with slow
destruction of CD4+ T cells all the while
Over a period of years, the CD4+T cell population
steadily declines
The final “crisis phase” shows catastrophic breakdown of
host defense, marked viremia and clinical disease.

70
1. More than 500 cells/µL – asymptomatic
2. Between 200 and 500 cells/µL – early symptoms
3. Less than 200 cells/µL – severe immunological
suppression.
CD4+ cell count indicates status of patient’s disease,
while viral load measurements provides prognosis.
Most patients develop AIDS after a chronic phase lasting
7 -10 years
Rapid progressors – chronic phase lasts for only 2-3 years
after primary infection
Nonprogressors – chronic phase lasts for 10 years or
more
71
Severe immunodeficiency manifested by
Opportunistic infections (accounts for 80% of deaths)
with organisms such as Pneumocystitis jiroveci (formerly
carinni), cytomegalovirus, Mucor species, and typical
and atypical mycobacteria;
Other opportunistic infections frequently found include
Candida, Cryptosporidium, Coccidiodes, Cryptococcus,
Toxoplasma, Histoplasma, and Giardia infections.
Increased incidence of malignancy, particularly multifocal
Kaposi’s sarcoma, and B- cell non-Hodgkin’s lymphoma;
hepatocellular carcinoma.
Central and peripheral nervous system manifestations occur
due to opportunistic infections, CNS tumors, or direct
neural infection with HIV. 72
73
74
ELISA ( sensitive, high false positive rate,
RULE OUT test), positive results are confirmed
with western blot assay (specific, high false
negative, RULE IN test). These tests look for
antibodies to viral proteins.
HIV PCR / Viral load tests.

75
Amyloidosis refers to a variety of conditions in which
amyloid proteins are abnormally deposited in organs
and/or tissues.
The amyloid protein is misfolded and changes its
configuration to insoluble form, from its normal soluble
form when not misfolded.
Its staining characteristics resemble starch (amylose),
hence the name amyloid
Amyloid is not a single substance but a group of
substances (about 20) that share a common physical
structure.
It always has a β- pleated sheet configuration.
Amyloid always begins extracellularly
Characteristically stained by Congo red dye 76
May be localized or systemic; Systemic consists of:
1. Primary amyloidosis (immunocytic dyscrasia amyloidosis)
– e.g. Multiple myeloma
Deposition of amyloid light chains (AL protein) – They
are localized as nodules.
In Lung, larynx, tongue, skin, urinary bladder
2. Secondary amyloidosis (reactive systemic amyloidosis)
Composed of Amyloid associated (AA protein)
Kidney, liver, adrenals, pancreas, lymph nodes and
spleen. It occurs as a complication of chronic
inflammation.
May occur in association with renal cell carcinoma and
Hodgkin’s lymphoma
3. Hereditary or familial amyloidosis – rare, e.g. familial
mediterranean fever 77
78