Immunology

presentation outline
 Objective of the study
 Defntion
 Types
 Role
 Antibodies
 immune Failure
objectives

At the end of the lectur student will

 define immunity

 classify there type

 explan there role

 define antibody

 understand immune failure

 Definition
• Immune system = cells, tissues, and molecules that mediate
resistance to infections

• Immunology = study of structure and function of the immune system

• Immunity = resistance of a host to pathogens and their toxic effects

• Immune response = collective and coordinated response to the

introduction of foreign substances in an individual mediated by the
cells and molecules of the immune system
Role of the immune system

• Defense against microbes

• Defense against the growth of tumor cells
• kills the growth of tumor cells
• Homeostasis
• destruction of abnormal or dead cells
(e.g. dead red or white blood cells, antigen-antibody complex)
Two types of immunity
1. Innate (non-adaptive)
• first line of immune response
• relies on mechanisms that exist before infection

2. Acquired (adaptive)
• Second line of response (if innate fails)
• relies on mechanisms that adapt after infection
• handled by T- and B- lymphocytes
• one cell determines one antigenic determinant
Innate immunity: mechanisms
• Mechanical barriers / surface secretion
• skin, acidic pH in stomach, cilia
• Humoral mechanisms
• lysozymes, basic proteins, complement, interferons
• Cellular defense mechanisms
• natural killer cells neutrophils, macrophages,, mast cells, basophils,
eosinophils
Adaptive immunity/second line of response
• Based upon resistance acquired during life
• Relies on genetic events and cellular growth
• Responds more slowly, over few days
• Is specific
• each cell responds to a single epitope on an antigen
• Has anamnestic memory
• repeated exposure leads to faster, stronger response
• Leads to clonal expansion
• Can be active or passive
 Active Immunity Passive Immunity
Natural clinical, sub-clinical via breast milk, placenta
infection

Artificial Vaccination: immune serum, immune cells

Live, killed, purified
antigen vaccine
 Cont…..
• Cell-mediated immune response (CMIR)
• T-lymphocytes
• eliminate intracellular microbes that survive within phagocytes or other
infected cells
• Humoral immune response (HIR)
• B-lymphocytes
• mediated by antibodies
• eliminate extra-cellular
microbes and their toxins Plasma cell
(Derived from B-
lymphocyte, produces
antibodies)
Cell mediated immune response
Primary response
• production of specific clones of effector T cells and memory clones
• develops in several days
• does not limit the infection
Secondary response
• more pronounced, faster
• more effective at limiting the infection
Humoral immune response
 B lymphocytes recognize specific antigens
• proliferate and differentiate into antibody-secreting plasma cells
 Antibodies bind to specific antigens on microbes; destroy microbes via specific
mechanisms
 Some B lymphocytes evolve into the resting state - memory cells
Antibodies (immunoglobulins)
 Belong to the gamma-globulin fraction of serum proteins
 Y-shaped or T-shaped polypeptides
• 2 identical heavy chains
• 2 identical light chains
Five kinds of antibodies
• IgG, IgM, IgA, IgD, IgE
 IgM
Secreted initially during primary infection
Cannot cross the placenta
Major functions / applications
• secreted first during primary exposure
• activates the complement
• used as a marker of recent infection
 IgA
• Monomeric in serum
• Dimeric with secretory component in the lumen of the gastro-
intestinal tract and in the respiratory tract
• Major function / application
• neutralizes microbes and toxins
 IgD

• Monomeric
• Major functions / applications
• present on the surface of B lymphocytes
• functions as membrane receptor
• has a role in antigen stimulated lymphocyte differentiation
 IgE

• Mediates type I hypersensitivity

• Monomeric
• Major functions / applications
• associated with anaphylaxis
• plays a role in immunity to
helminthic parasites
 IgG

• produced after IgM

• higher levels persist in small amounts throughout life
• produced in large amounts during secondary respons
• persistence of antigen sensitive ‘memory cells’
after primary response
 Anamnestic
response
Antibody titer

IgG

IgM

Time

First stimulus Second stimulus

IgM – IgG sequential response

Failure of immune response
1. hypersensitivity reactions
Cause cell damage through excessive immune response to antigens
• Hypersensitivity
overreaction to infectious agents
• Allergy
overreaction to environmental substances
• Autoimmunity
• overreaction to self
2. immunodeficiency

• Loss or inadequate function of various components of the immune

system
• Can occur in any part or state of the immune system
• physical barrier, phagocytes, B lymphocytes, T lymphocytes,
complement, natural killer cells
• The immuno-compromised host
• has an impaired function of immune system
• is at high risk of infection
 Cont...
It can be
1. Congenital (primary) immunodeficiency
• genetic abnormality
• defect in lymphocyte maturation
2. Acquired (secondary) immunodeficiency
• results from infections, nutritional deficiencies or treatments
• AIDS, chronic leukemia
 cont...

Disorder Compromised function

Altered anatomic Mucus membrane Reduction in IgA Microbe binding
barrier
Gastro-intestinal tract Elevated pH Bacteria killing

Change in flora Colonization resistance

Immune system Innate immunity Reduction of complement Activates phagocytosis

Opsonization of bacteria
Membrane attack complex

Neutropenia Phagocytosis
Monocytopenia Bacteria killing

Adaptive immunity Reduction of T cells Activation of macrophages

Activation of B lymphocytes

Hypo-gammaglobulinemia Neutralizes pathogens and

toxins, opsonization,
complement activation
HIV AIDS
 Eipedmology

• HIV infection/AIDS is a global pandemic, with cases reported

from virtually every country.
• At the end of 2016
an estimated 36.7 million individuals were living with HIV infection.

 An estimated 95% reside in low- and middle-income countries

 ~50% are female, and 2.1 million are children <15 years
An estimated 1.8 million new cases of HIV infection occurred
worldwide.
About one third of new infections were among people age 15–24 years.
Epidemology
 VIROLOGY

• Outer lipid-containing membrane = gp120 ( envelope protein ) & gp41

( transmembrane protein)

• Inner membrane ( Matrix protein) = p17

• A capsid with a dense inner core ( p24 core Ag ).

• The core contains two identical copies of the ss RNA genome.

• The RNA molecules are complexed with enzymes: reverse
transcriptase (P64), integrase ( p12) )
Cont....
 LIFE CYCLE

• Six steps
1. entry (binding and fusion)
2. reverse transcription(in 24 hours)
3. Integration
4. replication (transcription and translation)(72 hours)
5. assembly
6. budding and maturation
 Cont...

1. Entry (Attachment /binding/):- fusion of the virus to the host cells

• The receptor and co-receptors of CD4 cells interact with HIV’s gp-120
and gp-41 proteins during entry into a cell and release of Viral RNA into
the cytoplasm of the host cell.

Co-receptors for CD4 molecule for viral fusion and entry into target cell

• CCR5 - Co-receptor of monocytes/macrophages

• CXCR4 - Co-receptor of T cells

 Cont..
2. Reverse transcription:- Viral RNA is concerted in to Double stranded DNA by reverse
transcriptase enzyme
3. Integration of viral DNA to host-cell DNA
4. Replication: Cellular activation causes transcription (copying) of HIV DNA back to
RNA
5. Viral Assembly: HIV assembled under cell membrane and buddes from cell (by
protease enzyme)
6. Release and Maturation : viral Proteases enzymes cleave longer proteins in to
important viral proteins and help to convert immature viral particle into an infectious
HIV
Cont....
 TRANSMISSION

Sexual intercourse
Blood and blood products
Mother to child/ perinatal/ vertical
Contaminated medical equipment's, traditional materials
Sexual intercourse is the major route of transmission of HIV throughout
the world.
The precise risk of HIV transmission from one act of sexual intercourse
with an infected person is not known
 OCCUPATIONAL TRANSMISSION OF HIV
Exposures that place a health care worker at potential risk of HIV infection are

• percutaneous injuries (e.g., a needle stick or cut with a

sharp object) or

• contact of mucous membrane or non intact skin (e.g.,

exposed skin that is chapped, abraded, or afflicted with dermatitis)

with blood, tissue, or other potentially infectious body fluids.

 Cont..

• The risk of HIV transmission following skin puncture is ~0.3% and after a

mucous membrane exposure it is 0.09% if the injured and/or exposed

person is not treated within 24 h with antiretroviral drugs.

• Exposure through intact skin have not been shown to cause

transmission.
 Cont...
• Potentially infectious fluids
 Blood, Seminal fluid, Vaginal secretion

 Body fluids:
 CSF
 synovial fluid,
 pleural fluid,
 peritoneal fluid
 pericardial fluid
 amniotic fluid.
 Breast milk, Pus

• Saliva ,Tear , Sweat ,Vomitus , Sputum ,Nasal secretion, Stool &Urine

are not considered potentially infectious unless they are visibly bloody.
 Cont....
• The probability of MTCT of HIV ranges from 15 to 25% in industrialized
countries and from 25 to 35% in developing countries
• The relative proportions of MTCT were 23–30% before birth, 50–
65% during birth, and 12–20% via breast-feeding.
• PMTCT includes
• Preventing new HIV infection among woman of reproductive age

• Preventing unintended pregnancy woman living with HIV

• Preventing HIV transmission from a woman living with HV to hear baby

• Providing appropriate treatment, care and support to mothers living with HIV and children and

family.
 Cont…
• Factors that decrease risk of transmission
• Male circumcision
• HAART
• Treatment of STI
• PEP
PATHOGENESIS
 NATURAL HISTORY OF HIV
INFECTION
 Cont...
• Phase 1: Transmission
• Phase 2: Acute retroviral syndrome
• IP- 2-6 weeks post exposure
• HIV antibody negative
• CD+4 T cells number and function decline
• high viremia, high HIV RNA levels and P24 antigen
• Period of extreme infectiousness
• Be aware of false negatives
 Cont...
• Phase 3: HIV Sero-conversion

Window Period

• Time period between acquisition of HIV infection and antibody production

• Sero-conversion usually occurs with in 6 weeks to 3 months after

transmission
 Cont...
Phase 4: Latent infection (Clinical latency)
Asymptomatic stage

Period of continued viral replication and gradual decline in CD4 + cells

No virologic latency

PHASE 5…AIDS
 Cont..
• Direct detection of virus
• Viral Load: for Rx response monitoring.
• Reliable to 50 copies/mL of HIV RNA r DNA PCR
• P24 antigen detection in the early phase (2 weeks), during the window
period/ before sero-conversion
– applicable for early infant Dx
• Detection of Antibody
• Rapid tests= routinely used
• do not detect HIV in the “window period.”
• ELISA
• Western blot… confirmatory
 WHO CLINICAL STAGING

• CLINICAL STAGE 1
Asymptomatic infection
Persistent generalized lymphadenopathy (PGL)
 Enlarged lymph nodes > 1cm,in 2 or more non-contiguous extra-inguinal
sites, in absence of known cause; lasting more than 3 month
 CLINICAL STAGE 2

• Unexplained Weight loss <10% of presumed body weight

• Minor mucocutaneous manifestations:
• Papular pruritic eruptions ( PPE)
• Seborrhoeic dermatitis
• Angular chelitis
• Fungal nail infections of fingers
• Recurrent oral ulcerations (≥ 2 x/6months)
• Herpes zoster (current or in last 2 years)
• Recurrent upper respiratory tract infections (sinusitis, otitis media, bronchitis,
pharyngitis)
HERPES ZOSTER
SEBORREIC DERMATITIS
 CLINICAL STAGE 3
Oral candidiasis
Unexplained Weight loss >10%
Unexplained chronic diarrhoea > 1 month
Unexplained prolonged fever (intermittent or constant for >1 month)
Recurrent vaginal candidiasis
Oral hairy leukoplakia ( OHL )
Pulmonary tuberculosis
 Cont...
Severe presumed bacterial infections (e.g. pneumonia, empyema,
pyomyositis, bone or joint infection, meningitis, bacteremia)
Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
• Unexplained:
• Anaemia (<8g/dl) or
• Neutropenia (<500/mm³) or
• Thrombocytopenia (<50 000/mm³)
(for > 1 month)
 CLINICAL STAGE 4

Recurrent severe bacterial pneumonia

Chronic herpes simplex infection- orolabial, genital, or anorectal of >
1 month duration
Cytomegalovirus infection (other than liver, spleen, LN)

CNS toxoplasmosis
Cryptococcal meningitis (or other extra pulmonary crypto)
Extrapulmonary tuberculosis
HIV encephalopathy
Progressive multifocal leukoencephalopathy (PML)
 cont...
Pneumocystis pneumonia ( PCP)

Candidiasis of esophagus, trachea, bronchi, or lungs

Any disseminated endemic mycosis ( Histoplasmosis, Coccidiomycosis,

Penicilliosis )

Kaposi's sarcoma
HIV WASTING SYNDROME
Weight loss >10% plus unexplained chronic diarrhea for 1 month or unexplained
chronic fever for 1 month.
 Cont....
Invasive cervical carcinoma

Cryptosporidiosis, Isosporiasis

Disseminated Mycobacterial diseases other than tuberculosis

Recurrent non-typhoidal salmonella septicaemia (2 or >episodes in one year)

Lymphoma (cerebral or B-cell non-Hodgkin)

viseral Leishmaniasis

Visceral Herpes simplex

HIV Enteropathy
 Management
HAART

• GOALS OF HAART

Decrease risk of opportunistic infections

• Improves quality of life

• Decrease risk of transmission

• Prolong life
 ANTIRETREOVIRAL DRUGS

• 5 classes
1. Nucleoside reverse transcriptase inhibitors
(NRTI)
2.Non nucleoside reverse transcriptase inhibitors(NNRTI)
3.Protease inhibitors
4. Entery inhibitors
5.Integrase inhibitors
 WHEN TO START ART

• ART should be initiated in all adults living with HIV at any CD4 cell
count.
• Pretreatment evaluation
• Adherence counseling
• Screen and treat OI
• Baseline lab CBC,CD4 count, Liver and renal function test, Hbsag if
available.
 cont...
FIREST LINE ALTERNATIVE FIREST LINE

TDF+3TC+EFV is preferred for TB HIV co

TDF+3TC+EFV TDF+3TC+NVP infection.
When apatient is co infected with HBV, the
AZT+3TC+EFV regimen should contain TDF+3TC.

AZT+3TC+NVP

ABC+3TC+EFV
 ART MONITORING

• CD4 monitoring: median CD4 increase is 100-200 in the first year after
initiation of ART(in adherent patients)
• With low baseline CD4 ,the increment in CD4 may be much slower.
• CD4 frequency of testing : at base line and every 6months

• Viral load: do after 6 months of initiating ART and every 12 months then
after.

• T-staging is the clinical method of monitoring ART.

Cont...
Cont..
Cont...
 Common adverse effects of ARVs

3TC&FTC :SAFE drugs

AZT: GI intolerance, anemia (macrocytic), neutropenia, lactic acidosis,
myopathy
TDF: renal toxicity
ABC: hyper sensitivity
EFV: CNS toxicity, rarely severe skin reactions
NVP: skin reactions, hepatitis, hypersensitivity reaction
Protease inhibitors: lipohypertrophy, glucose intolerance, diarrhea,
pancreatitis, hepatitis
cont...
 DEFINITIONS OF TREATMENT FAILURE
1. Clinical failure: new or recurrent WHO stage 4 condition

2) Immunologic failure

persistent CD4 levels < 100 cells/microliter OR

CD4 <250/microliter following clinical failure

3) Virologic failure: plasma viral load > 1,000 copies/ml

NB: treatment failure is defined after 6 months of HAART

Reading assignment
• OPPORTUNISTIC INFECTIONS
• Immune Reconstitution Inflammatory Syndrome(IRIS)
 Thanks
and take care of your self from this stupid virus