Clinical immunology

2. •IMMUNODEFICIENCY DISEASES
•AUTOIMMUNE DISORDERS
•HYPERSENSITIVITY REACTIONS
GUIDED BY:
DR. AARTI TYAGI
DR. SABA HASSAN SHAH
PRESENTED BY:
DR. DEEPTI SINGLA
DR. AYUSH KUMAR
DR. MANVI BHARDWAJ

4. I. Immunodeficiency
II. Primary Immunodeficiency
III. Secondary Immunodeficiency
IV. AIDS
i. History of AIDS
ii. Origin of AIDS Virus
iii. HIV-1
iv. Transmission of HIV-1
v. Testing for HIV-1
vi. Treatment of HIV/AIDS

5.  The immune system is subject to failure of some or all
of its parts.
 If the system is not able to protect the host from
disease-causing agents or from malignant cells, an
immunodeficiency results.
 There are two types of immunodeficiency: Primary
and Secondary or acquired.

6.  Primary immunodeficiency results from a
genetic or developmental defect of the immune
system. The condition is present at birth, though it
may not manifest itself until later in life.
 Secondary (acquired) immunodeficiency is the
loss of immune function that results from exposure
to various agents. The most common example is
AIDS or acquired immunodeficiency syndrome,
which results from infection with the HIV-1 or
human immunodeficiency virus 1.

7.  Primary Immunodeficiencies may affect either adaptive
(T or B cells) or innate (macrophages or complement)
immune functions, which enables us to categorize them
according to the type of developmental stage of the cells
involved.
 So, lymphoid cell disorders may affect T cells, B cells, or,
in combined immunodeficiencies, both B and T cells.
Myeloid cell disorders affect phagocytic function.

9.  May involve B cells, T cells, or both of these
Lineages.
 B-cell immunodeficiency disorders cause
recurrent bacterial infections.
 T-cell deficiency though, can affect both
humoral and cell-mediated responses.
SCID: Severe Combined Immunodeficiency
WAS: Wiskott - Aldrich syndrome
Interferon-Gamma-Receptor Defect
X-Linked Agammaglobulinemia
X-Linked Hyper-IgM Syndrome
CVI: Common Variable Immunodeficiency
Ataxia Telangiectasia
Immune Disorders Involving the Thymus

10.  Defects in cell interaction and signaling can lead to
severe immunodeficiency.
 A number of primary immunodeficiencies are rooted
in defects in these interactions.
SCID is an example.

11. They affect the innate immune functions. Most
of them result in impaired phagocytic processes
that are manifested by recurrent
microbial infection of greater or lesser severity.
1. Reduction in Neutrophil Count
2. CGD: Chronic Granulomatous Disease
3. Chediak-Higashi Syndrome
4. LAD: Leukocyte Adhesion Deficiency
 Defects in the Complement Lineage:
Many complement deficiencies are associated with
increased susceptibility to bacterial infections
and/or immune-complex diseases.

13.  Although there are no cures for immunodeficiency
disorders, there are various treatment possibilities. In
addition to complete isolation from exposure to any
microbial agent, treatment options for the
immunodeficiencies include:
1) Replacement of a missing protein
2) Replacement of a missing cell type or lineage
3) Replacement of a missing or defective gene

14.  Loss of immune function that results from
exposure to various agents.
 Acquired Hypogammaglobulinemia
Recurrent infection that manifests itself in young
adults. There are usually very low levels of total
immunoglobulin, though T-cell numbers and
function may be normal. It is treated with
gammaglobulin therapy.
 Agent-Induced Immunodeficiency
Results from exposure to any of a number of
chemical and biological agents that induce an
immunodeficient state.
 AIDS: Acquired Immunodeficiency Syndrome

15.  AIDS was first reported in the United States in 1981
in Los Angeles, New York, and San Francisco.
 The first patients displayed unusual infections by
opportunistic agents, such as Pneumocystis
carinii, which causes PCP or P. carinii pneumonia,
as well as other rare opportunistic infections.
 Opportunistic agents are microorganisms that
healthy individuals can harbor with no ill
consequences but that cause disease in those with
impaired immune function.

16.  Within a few years after recognition of AIDS, the causative
agent was discovered to be a retrovirus, Human
Immunodeficiency Virus 1, HIV-1.
 There is another human virus known as HIV-2, which is less
pathogenic than HIV-1. It infects non-human primates that are
not infected by HIV-1.

17.  The virus that causes AIDS
 It is a retrovirus with two
copies of single stranded RNA
genome.
 It uses reverse transcriptase
to transform its ss-RNA
genome into a ds-DNA for
integration into its host
genome.
 It has marker proteins (gp120)
in the protein coat that allow
it to recognize specific cells in
the human body.
 The protein coat also contains
MHC-I and MHC-II
molecules.

18.  HIV gp120 surface protein binds
CD4 on target cell.
 Transmembrane component,
gp41, binds coreceptor CXCR4 to
enhance fusion.
 Viral genome and other proteins
are able to enter the cell via
nucleocapsid.
 RT transcribes the ssRNA
genome.
 The next DNA strand is made,
making a double stranded DNA
molecule called a provirus.
 The dsDNA is transferred to the
nucleus to be added to the host
genome via the viral integrase
protein at HIV LTR sites.

19.  In a latent cell, the
integrated provirus must be
activated by transcriptional
factors to make genomic
ssRNA and mRNAs.
 Genomic RNA is exported.
 Host ribosomes transcribe
viral mRNAs, and the
proteins are either with the
genomic RNA or part of the
membrane.
 The membrane buds to
form a viral envelope.
 The mature virus is released
outside the cell.

20. HIV infection progresses in three stages: acute HIV infection, chronic HIV
infection, and AIDS. During acute infection, HIV multiplies rapidly. As acute HIV
infection progresses to chronic HIV infection, HIV multiplies less rapidly and HIV
levels drop. However, as chronic HIV infection advances, HIV levels increase and
the number of CD4 cells decreases. Declining CD4 cell levels indicate increasing
damage to the immune system and advancement towards AIDS.

21.  Enzyme-linked immunosorbent assay (ELISA). This
screening test is usually the first test used to detect infection
with HIV.
 Western blot. It is more difficult than the ELISA to perform and
interpret accurately, but it is less likely to give a false-positive
result because it can distinguish HIV antibodies from other
antibodies that may react to the ELISA. A Western blot is usually
done to confirm the results of two positive ELISA tests.
 Indirect fluorescent antibody (IFA). Like a Western blot test,
it is used to confirm the results of an ELISA.
 Polymerase Chain Reaction (PCR). This test detects the RNA
of HIV, rather than detecting antibodies to HIV. Therefore, PCR
can reveal an HIV infection before antibodies can be detected.
PCR can also accurately determine whether a baby born to an
infected mother has HIV.

22. 3 Points In HIV Cell Cycle Where Replication Can be
Stopped:

23.  3 primary methods to battle HIV/AIDS:
 Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
 Non-Nucleoside Reverse Transcriptase Inhibitors
(NNRTIs)
 Protease Inhibitors

24.  Reverse Transcriptase Inhibitors interfere with the
reverse transcriptase (RT) enzyme that HIV needs
to make copies of itself.
 There are 2 types of inhibitors each working
differently.
Type 1: NRTI’s – Nucleoside drugs provide faulty
DNA building blocks, stopping DNA chain, which virus
uses to make copies of itself.
Type 2: NNRTI’s- Non-nucleoside RT inhibitors
binds to RT enzyme so that virus cannot carry out its
copying function.

25.  Protease Inhibitors (PI), discovered in 1995,
blocks the protease enzyme.
 When protease is blocked, HIV makes copies of
itself that can’t infect the new cells.
All these 3 combine to form Highly active
antiretroviral therapy (HAART) which has proven to
be much more effective against HIV’s mutations.