This document provides an overview of immunological disorders and HIV/AIDS. It discusses the components of the immune system including innate and adaptive immunity. It describes the four types of hypersensitivity reactions and common disorders like allergies. It then focuses on HIV/AIDS, explaining how it weakens the immune system, the types of HIV, modes of transmission including sexually, blood-to-blood contact, and from mother to child, as well as the pathogenesis and clinical manifestations of HIV infection.

1. UNIT VI:
Immunological Disorders
By:
Ms. Kiran Sayani
Nursing Instructor
SBSON

2. Objectives
By the end of the session, students will be able to:
• Review the following concepts of immune response:
• Components of immune response
• Humoral versus cell mediated immunity
• Antigen processing presentation and recognition
• Immediate and delayed hypersensitivity
• Discuss the disorder of immune response including. AIDS
(Acquired Immunodeficiency syndrome) & Hypersensitivity
(allergies)
• Discuss the epidemiology, pathogenesis & clinical manifestation
of HIV infection.
• Discuss the pathophysiology of different types of hypersensitivity
(Type I, Type II, Type III & Type IV)

3. Immunity
• Immunity can be defined as the body’s ability
to defend against specific pathogens and/or
foreign substances in the initiation of disease
processes.
• The multidimensional response initiated by the
body’s various defense systems is known as
the immune response.

4. Types of Immunity
• Innate immunity
• Adaptive immunity
• They are complementary processes that work
to protect the body.

5. Innate Immunity
• Also called natural immunity
• The body’s 1st and 2nd line of defense, occurs
early and more rapidly in response to foreign
substances.
• Intact innate immune mechanisms are essential
for the initiation of the adaptive immune response
and, therefore, a successful immune response
dependent upon cooperation between the two
systems.

6. Continued
The major effector components of innate immunity includes:
• Epithelial cells (skin), which block the entry of infectious
agents
• Phagocytic neutrophils and macrophages, which engulf
and digest microbes
• The complement system, which increases the
inflammatory response and uses the membrane attack
response to lyse microbes.

7. Function of Innate Immunity
• The innate immune system uses pattern
recognition receptors that recognize microbial
structures only (e.g., sugars, lipid molecules,
proteins) that are shared by microbes and are
often necessary for their survival, doesn’t matter
that it is harmful or not but are not present on
human cells.
• The innate immune system is able to distinguish
between self and non-self, but is unable to
distinguish between agents.

8. Adaptive Immunity
• Adaptive immunity (also called acquired
immunity) refers to immunity that is acquired
through previous exposure to infectious and
other foreign agents.
• It is usually delayed unless the host has been
exposed before.

9. Continued
• A defining characteristic of adaptive immunity is
the ability not only to distinguish self from non-self
but to recognize and destroy specific foreign
agents based on their distinct antigenic
properties.
• The components of the adaptive immune system
are the T and B lymphocytes and their products.

10. Immune System
• Dendritic cells are an essential component of both innate and
adaptive immunity and serve as the link between the two
immune responses through the release cytokines and
chemokines.
• As a result, innate immune cells are capable of
communicating important information regarding key
characteristics of the invading microorganism or foreign
substance to the B and T lymphocytes involved in adaptive
immunity.
• The adaptive immune response is also capable of increasing
its efficiency by recruitment and activation of additional
phagocytes and molecules of the innate immune system.

11. Cytokines and Their Role in Immunity
• Communicate critical information with each other.
• Chemokines are a subset of cytokines that
consist of small protein molecules involved in
both immune and inflammatory responses.
• They are responsible for directing leukocyte
migration to areas of injury and to locations
where primary immune responses are initiated.

12. Third Line Of Defense
There are two types of adaptive immune responses,
that function to eliminate different types of Microbes.
• Humoral immunity
• Cell-mediated immunity

13. Humoral Immunity
• Humoral immunity is mediated by the B
lymphocytes (B cells) and is the principal defense
against extracellular microbes and their toxins.
• The B cells differentiate into antibody- secreting
plasma cells.
• The circulating antibodies interacts and destroys
the microbes that are present in the blood or
mucosal surfaces.

15. Cell Mediated
• Cell-mediated, or cellular, immunity is mediated
by the cytotoxic T lymphocytes (T cells) and
functions in the elimination of intracellular
pathogens (e.g., viruses).
• T cells develop receptors that recognize the viral
peptides displayed on the surface of infected cells
and then signal destruction of the infected cells.

18. • Antigens: Large complex molecules
(proteins/polysaccharides) that the immune
system recognizes as foreign found on the cell
membrane of micro organisms in the blood
plasma/interstitial fluid
• Antibodies: A protein produced by lymphocytes
in response to the entry of an antigen in the
body.
• Immune Response: Interaction between
antibody & antigen which result in the antigen
being eliminated from the body

19. Primary & Secondary Immune
Response

21. Cells & Molecules of immunity
Response
Cells
• Lymphocytes
 B Lymphocytes
 T Lymphocyte
• Antigen presenting cells(APCs)
Molecules
• Major Histo compatibility Complex
• CD(clusters of differentiation)
 CD4
 CD8

22. Lymphocytes
• B Lymphocytes (B cells):They get mature in the
bone marrow, and are responsible for antibody
mediated immune response.
• T lymphocytes (T cells):-They get mature in the
thymus gland, and are responsible for cell mediated
immune response. There are 4 types of T cells
• Both T & B are found in lymph nodes, spleen, skin
and mucosal surface.

23. Types of T Lymphocytes
• Cytotoxic or killer T cells: Do their work by releasing
lympho-toxins, which cause cell lysis
• Helper T cells: Serve as managers, directing the immune
response (e.g. B cells)
• Suppress or T cells: Inhibit the production of cytotoxic T
cells when they are not needed.
• Memory T cells: Are programmed to recognize and
respond to a pathogen once it has invaded and been
repelled.

24. MHC (Major Histo Compatibility
Complex)
• The external surfaces of all non-immune cells of the
body are dotted with a huge variety of protein (self-
antigens). Amongst these a specific group of
glycoprotein are called MHC proteins (self-antigens).
There are two types of MHC molecules:
• MHC-I
• MHC-II

25. Antigen Presenting Cells (APCs)
• APC acts as antigen presenters. They engulf foreign
particle (antigens) and present fragments of these
antigens, like signal flags, on their own surfaces. These
AP are located strategically at locations where antigens
are likely to penetrate,
• e.g. epidermis, Mucus Membrane and lymph nodes.
APC include:
• Macrophages,
• B lymphocyte
• Dendritic cells.

26. CD (clusters of differentiation)
• T& B cell display additional membrane molecules
called CD molecules. These molecules support the
function of immune cells and also serve to define
functionally distinct sub sets of cells such as:
• CD 4 helper T cell
• CD 8 cytotoxic T cells

27. Mechanism To Destroy Antigens
• Agglutination: The clumping of antigens easy targets for
phagocytes to destroy.
• Neutralization: Toxin are made non-toxic by reaction with
the antibodies
• Lysis: Lysin (antibodies) bind to antigens cause
antigens/pathogens to rupture
• Opsonization: The binding of antibodies to antigens
stimulate phagocytes (macrophage) to destroy the antigens.

28. Immune Disorders
• Allergy (exaggerated against environmental antigens)
• Autoimmunity (misdirected against host’s own cells)
• Allo immunity (directed against beneficial foreign tissue
e.g. transplants or transfusions)
• Immunodeficiency (insufficient protection)
• The inappropriate immune responses of allergy,
autoimmunity, and allo immunity can be collectively
classified as Hypersensitivity

29. Hypersensitivity Reactions
• Over reaction of the immune system to harmless
environmental antigens
• Altered immunological reactivity to an antigen that
results in a pathologic immune response after re-
exposure
• Undesirable (damaging, discomfort-producing)
reactions produced by the immune system

30. Types of Hypersensitivity Reactions
• There are 4 type of hypersensitivity reactions.
• Type I: Classical immediate hypersensitivity
• Type II: Cytotoxic antibody mediated hypersensitivity
• Type III: Immune-complex mediated hypersensitivity
• Type IV: Cytotoxic hypersensitivity

32. TYPE-I
• It is mediated by IgE antibodies and requires previous
exposure to specific antigen. It usually affects on skin,
lungs and gastro-intestinal tract
• The symptoms resulting from allergic responses are
known as anaphylaxis. Depending upon portal of entry it
can be systemic (generalized), or cutaneous (localized).
• Includes: Hay fever, asthma, eczema, food allergies.

33. Continued
• Exposure to the allergen can be through inhalation,
ingestion, injection, or skin contact.
• Mast cells, basophils, and eosinophils are essential to
the development of type I hypersensitivity reactions.
• They are members of the granulocyte class of leukocytes
because they contain granules rich in chemical
mediators such as histamine and heparin.

34. Pathology of Type- I Reaction
• By an antigen stimulated type 2 helper (T2H) T cell leads
to plasma cell production of IgE and mast cell
sensitization.
• Subsequent binding of the antigen produces degranulation
of the sensitized mast cell with release of preformed
mediators that leads to a primary or early-phase response.
• T2H (T-cell) recruitment of eosinophils, along with the
release of cytokines and membrane phospholipids from
the mast cell, leads to a secondary or late-phase
response.

36. Anaphylactic (Systemic) Reactions
• Anaphylaxis is systemic life-threatening IgE mediated
hypersensitivity reaction associated with the widespread
release of histamine into the systemic circulation that
produces massive vasodilation, hypotension, arterial
hypoxia, and airway edema.
• It can be converted into anaphoric shock which is not just
difficult to treat but life threading as the body volume for
survival is compromised hence lead to major multi failure
of organs.

37. Clinical Manifestations
• It can be graded on a scale of I to IV.
• Grade I reactions are usually confined to the cutaneous
and mucosal tissues manifesting as:
 Erythema
 urticaria,
 with or without angioedema.

38. Grade II
Grade II reactions progress to include moderate
multisystem signs such as:
• Hypotension
• Tachycardia
• Dyspnea
• Gastrointestinal disturbances (e.g., nausea, vomiting,
diarrhea, abdominal cramping from mucosal edema).

39. Grade III
Grade III reactions become life threatening because of
the development of:
• Bronchospasm
• Cardiac dysrhythmias
• Cardiac collapse.

40. Grade IV
• Once a hypersensitivity reaction reaches
grade IV, cardiac arrest has occurred and
management is purely resuscitative in nature.

41. Type II, Antibody-Mediated Disorders
• Type II (antibody-mediated) hypersensitivity or cytotoxic
hypersensitivity reactions are mediated by IgG or IgM
antibodies directed against target antigens on specific
host cell surfaces or tissues.
• The antigens may be either intrinsic, inherently part of
the host cell or extrinsic, incorporated into the cell
surface upon exposure to a foreign substance or
infectious agent and result in cellular injury.
• These antigens are known as tissue-specific antigens.

42. Continued
• There are four general mechanisms by which type II
hypersensitivity reactions can be propagated, but
regardless of the pathway, it is always initiated by the
binding of IgG or IgM antibody to tissue-specific antigens.
• These mechanisms include complement-activated cell
destruction, antibody mediated cell cytotoxicity,
complement- and antibody-mediated inflammation, and
antibody-dependent modulation of normal cell surface
receptors

43. Pathology of Type-II
• Formation of the membrane attack complex (MAC) by
activation of C5-C9 allows the passage of ions, small
molecules, and water into the cell, causing direct lysis of
the cell. In addition, IgG and the complement fragment
C3b act as opsonins by binding to receptors located on
the cell surfaces of macrophages.
• This process activates the macrophages, which then
destroys the target cells by phagocytosis.
• Thus, activation of the complement system produces a two
fold response that culminates in cell destruction.

45. Examples
• Myasthenia Gravis
• Autoimmune Hemolytic Anemia

46. Type III, Immune Complex–Mediated
Disorders
• The antibody–antigen complexes are formed first in the
plasma and then deposited in the tissues.
• Type III, immune complex reactions involving
complement-activating IgG or IgM immunoglobulins with
formation of blood-borne immune complexes that are
deposited in tissues.
• Complement activation at the site of immune complex
deposition leads to attraction of leukocytes that are
responsible for vessel and tissue injury.

48. Continued
Activated complement generates vasoactive and
chemotactic mediators that causes tissue damage
through:
• Alteration in blood flow and vascular permeability
• Destructive action of inflammatory cells.
E.g. Arthus reaction, serum sickness, raymound
phenomena.

49. Type-IV Hypersensitivity
• Involve reactions by T cells (delayed type
hypersensitivity) memory cells.
• First contact sensitizes person, and subsequent
contacts elicit a reaction.
• The reactions are delayed by one or more days. Delay
is due to migration of macrophages and T cells to site
of foreign antigens.

50. Continued
Reactions are frequently displayed on the skin:
• Itching, redness, swelling, pain.
Examples:
• Tuberculosis skin test
• Poison ivy
• Metals
• Latex in gloves and condoms
• Anaphylactic shock may occur

51. Acquired
Immunodeficiency
Syndrome
(AIDS)

52. AIDS
Acquired Immune Deficiency Syndrome
• A= Acquired, not inherited
• I = Weakens the Immune system
• D= Creates a Deficiency of CD4+ cells in the immune
system
• S = Syndrome, or a group of illnesses taking place at
the same time

53. HIV and AIDS
• When the immune system becomes weakened
by HIV, the illness progresses to AIDS.
• Some blood tests, symptoms or certain
infections indicate progression of HIV to AIDS

54. Acquired Immuno-deficiency
Syndrome
• The acquired immunodeficiency syndrome (AIDS) is a
disease caused by infection with the human
immunodeficiency virus (HIV).
• Initially the syndrome was called GRIDS, for “gay-
related immunodeficiency syndrome” as it was found in
homosexual men.
• Lateral several hundred cases reported in all population
and the name was changed to acquired
immunodeficiency syndrome or AIDS

55. Types of HIV
• There are two types of HIV i.e. HIV-1 and HIV-2
• Transmitted through the same routes
• Associated with similar opportunistic infections
• HIV-1 is more common worldwide
• HIV-2 is found in West Africa, Mozambique, and Angola

56. HIV-2
• HIV-2 is less easily transmitted
• HIV-2 is less pathogenic
• Duration of HIV-2 infection is shorter

57. Transmission

58. Transmission of HIV Infection
• HIV is a retrovirus that selectively attacks the CD4+ T
lymphocytes.
• HIV infection have a deteriorating immune system and
thus are more susceptible to severe infections with
ordinarily harmless organisms.
• HIV is transmitted from one person to another through
sexual contact, blood-to-blood contact, intravenous drug
use or perinatally (pregnancy time).

59. Continued
• Transmission can occur when infected blood, semen, or
vaginal secretions from one person are deposited onto a
mucous membrane or into the bloodstream of another
person.
• Sexual contact is the most frequent mode of HIV
transmission.
• HIV is present in semen and vaginal fluids. There
• is a risk of transmitting HIV when these fluids come in
contact with a part of the body that lets them enter the
bloodstream.

60. Transmission To Child From Mother
• HIV may be transmitted from infected women to their
offspring in utero, during labor and delivery or
through breast-feeding.

61. Transmission to Health Care
Workers
• Occupational risk of infection for health care workers
most often is associated with percutaneous
inoculation (i.e. needle stick) of blood from a person
with HIV infection.
• Transmission is associated with the size of the
needle, amount of blood present, depth of the injury,
type of fluid contamination, stage of illness of the
person, and viral load of the person.

62. Causes
• Vaginal and anal mucosa,
• Superficial laceration,
• wounds, or sores on the skin.
• Contact with semen occurs during vaginal and anal
sexual intercourse.
• Oral sex
• Donor conception.
• Exposure to vaginal or cervical secretions occurs during
vaginal intercourse.
• Usage of same syringe/needles in contacted with HIV.
• Blood transfusion of HIV donor.

63. HIV is NOT Transmitted
• Shaking hands, body contact with infected
person
• Taking care of HIV patients.
• Eating and living with infected person.
• Mosquito and other insect bites.

64. Continued
• Sharing towels or clothes
• Swimming in the same pond, pool or river.
• Kissing or hugging
• Eating together.
• Caring for an infected person.
• Working & living with an infected person
• Using the same toilet

65. HIV-AIDS
• The HIV-infected person is infectious even when no
symptoms are present.
• The point at which an infected person starts to develop
HIV antibodies hence refer as positive HIV. This time is
called Seroconversion.
• The time after the contact with HIV and before
seroconversion is known as the window period. This is
about 1-6 months.

66. HIV and Immune System
• The CD4 cells coordinate a body’s immune response to
an invader (bacteria, virus, etc.)
• BUT, when HIV enters CD4 cells for reproduction, it
damages the CD4 cell, eventually killing it.
• The body’s immune system works hard making more
CD4 cells.
• Overtime, HIV destroys the CD4 cells faster than the
immune system can make new ones
• So, HIV damages the very system that usually protects
the body from infection.

67. HIV Disease
Progression of HIV disease is measured by:
CD4+ count
• Degree of immune suppression
• Lower CD4+ count means decreasing immunity
Viral load
• Amount of virus in the blood
• Higher viral load means more immune suppression

68. HIV Disease
• Severity of illness is determined by amount of virus
in the body (increasing viral load) and the degree of
immune suppression (decreasing CD4+ counts).
• Higher the viral load, the sooner immune
suppression occurs

70. Progression of HIV Infection
• HIGH viral load (number of copies of HIV in the
blood)
• LOW CD4 count (type of white blood cell)
• Increasing clinical symptoms (such as
opportunistic infections)

71. Direct infection by HIV infection
HIV can directly infect the systems:
• Brain (HIV dementia)
• Gut (wasting)
• Heart (cardiomyopathy)

72. Key Points
• HIV is a global pandemic and the number of people
living with HIV continues to increase worldwide.
• HIV epidemic is especially severe in resource-
constrained settings
• HIV is a virus that destroys the immune system, leading
to opportunistic infections.
• The progression from initial infection with HIV to end-
stage AIDS varies from person to person and can take
more than 10 years.

73. Epidemiology of HIV/AIDS
It is a Pandemic. The epicenter of pandemic is the Sub-
Saharan African countries .
Globally there are epidemic levels to estimate numbers of
people living with AIDS
• Concentrated Epidemic: HIV is concentrated in groups
with behaviors that expose them to a high risk of HIV
infection—such as people who inject drugs, sex
workers, or men who have sex with men.

74. • Generalized Epidemic: HIV is firmly established in the
general population estimated through regular
surveillance among pregnant women attending sentinel
antenatal clinics
• Women, biologically & socially more vulnerable in
comparison to men .
• Predominant mode of transmission in the world is sex
(Heterosexual).
• Transmission of infected blood and use of
contaminated needles /syringes is most efficient mode
of transmission

75. Epidemiology of HIV/AIDS in
Pakistan
Pakistan is currently experiencing concentrated HIV
infection epidemic. HIV prevalence of more than 5%has
been documented among high risk populations which
include:
• Injecting drugs users (IDUs)
• Men who have sex with men (MSM)
• Hijras (Male Transgender population)
• IDU predominant mode of transmission .

76. Risk factors for HIV/AIDS?
• Age (18 –45 years)
• Sexual Promiscuity (Multiple Sex Partners)
• Injecting Drug Use (IDUs)
• Frequent Travels
• Living away from family
• Being member of marginalized population
• Prosiners, Hijras, MSM, e.t.c
• Persons with Sexually Transmitted Infections

77. Pathogenesis of HIV-AIDS
• The HIV is a retrovirus that destroys the body’s immune
system by taking over and destroying CD4+ T cells.
• In the process of taking over the CD4+ T cell, the virus
attaches to receptors on the CD4+ cell, fuses to and
enters the cell, incorporates its RNA into the cell’s DNA,
and then uses the CD4+ cell’s DNA to reproduce large
amounts of HIV, which are released into the blood.
• As the CD4+ T-cell count decreases, the body becomes
susceptible to opportunistic infections.

79. Replication of HIV in CD4 T cells
(8 steps)
1. Attachment
• HIV virus binds to host cell with CD4 TCR (Helper T
cells) that has high affinity for HIV. gp120, gp41
envelope glycoproteins also attaches with the host cell.
2. Uncoating
• Viral envelope peptide fuse to the CD4 cell membrane
resulting in un-coating of the virus and the viral RNA
and 3 enzymes entering the host cell.

80. 3. DNA synthesis through Reverse transcriptase
• HIV virus convert its RNA into DNA by using enzyme
reverse transcriptase. The double stranded DNA carries
instruction for viral replication.
4. Integration
• New DNA enters nucleus of CD 4 cell and with the help
of intergase gets inserted into host cell DNA
5.Transcription
• It involves transcription of DNA to form copies of mRNA
with instruction to build new viruses or simply instruct he
host cell to make copies of HIV virus.

81. 6. Translation
• rRNA uses instruction on mRNA to create polyproteins
(components for construction of new viruses)
7.Cleavage
• Protease cuts the polyprotein chain into the individual
protein that will make up the new viruses.
8. In this step the proteins and the viral RNA are
assembled into new HIV virus particles and released from
CD4 cells to infect other CD4 cells.

82. Clinical Progression
Clinical symptoms will begin to develop at the end of this
period as CD4 count falls and viral load increases.
• May include
• Bacillary angiomatosis (lesion on skin caused by
infection with gram negative organism).
• Persistent or resistant vulvo-vaginal candidiasis
• PID (Pelvic inflammatory disorder).
• Cervical Dysplasia
• Hairy leukoplakia
• Herpes Zoster
• Fever or diarrhea lasting longer than one month

83. HIV Infection
• Primary HIV Infection (Acute Retroviral Syndrome)
• Seroconversion
• Asymptomatic HIV Infection
• Symptomatic HIV Infection (AIDS Stage)

84. Primary HIV Infection
(Acute Retroviral Syndrome)
• Incubation period two to four weeks.
• Very high viral load1,000,00 copies/ml
• CD4 cells decreases
• Vary from six days to six months.
• Flu like Symptoms
• Fever, Head Ache, Sore Throat, Skin
• Rash, Enlargement of Lymph-Glands.
• Self limiting Symptoms
• Disappear within one to two weeks.

85. Seroconversion
• Viral load decreases (controlled by immune
system) and remains at a lower level for several
months
• Window period (have unique opportunity for
treatment)
• Appearance of detectable Antibodies.
• Antibodies appear after six weeks to six months.
• Several methods to check HIV antibodies.

86. Asymptomatic HIV Infection
• Latent period
• No symptoms and signs of disease.
• Infected person looks perfectly all right.
• Varies six months to ten years.
• HIV virus continue to replicate.
• CD4 cell, count decrease from 800-1000 cells
/micro L to 200 cells.

87. Symptomatic HIV Infection
(AIDS Stage)
• Symptomatic stage starts once CD4 cells start falling to
less than 200cells/micro L
• With low levels of CD4 the risk of death and
opportunistic infections increases significantly.
• Without antiviral therapy this phase can lead to death in
2-3 years.

88. Development Of Opportunistic
Infections
• Candidiasis(Oral, Esophageal)
• Tuberculosis
• Pneumocystis carinii
• Toxoplasmosis
• Crypto-coccal Infection
• Mycobacterium avium
• Cytomegalovirus infection

89. AIDS Defining Illness
• Serve loss of weight
• Repeated Diarrhea
• Pneumocystis Carinii Pnemonia
• Oesophagal Candidiasis
• Kaposi’s Sarcoma
• Cryptoccocal Meningitis

90. HIV Vaccine
• It took 47 years, to develop a polio vaccine. Developing
an HIV vaccine is even more difficult. These are a few
reasons why:
• The HIV virus makes copies of itself very quickly.
• Many types of HIV exist, and new types continue to
arise.
• HIV has developed clever ways of "outwitting" the
immune system. Consequently, none of the people
infected by HIV have ever completely cleared it from their
bodies.
• Scientists are still trying to understand the specific ways
the immune system needs to respond to prevent HIV
infection

91. How HIV/AIDS Can be Prevented?
• Abstinence from sex (premarital sex)
• Being faithful to partner (avoid extramarital sex)
• Use condom for disease prevention
• Avoid sharing of needles, syringes proper screening of
blood before transfusion
• Use sterilized instruments and equipment

92. References
• Norris, T. L. (2019). Porth's pathophysiology:
Concepts of altered health states (10th Ed.).
Philadelphia: Wolters Kluwer.