This slide contains detailed information of the immunological response happens during the HIV infection in human

1. Immune Response to HIV
Infection
M.Narenkumar,
Dept.of Biotechnology,
Alagappa University,
Karaikudi, Tamilnadu

2. IMMUNITY
Adaption to the infective agent
Maintain the protective & Immune
tolerance
Innate immunity
TYPES
Adaptive immunity

3. Human Immunodeficiency
Virus-1
 Cause secondary
immunodeficiency
Targets T-cells
 Causative agent AIDS
 HIV-1 strain
 T-helper cells decrease

4.  Target: CD4+ cells
strong affinity
g120(coat protein) of HIV-1
• CD4+ & CXCR4 (OR) CCR5=Entry
T-cells Monocyte,
Macrophage

5. INITIAL INTERACTION
1st by Innate immunity- inactivate
antigen, induce adaptive immunity
Cells involved:
• Macrophage
• Dendritic cells
• NK cells
• Graulocytes

6. RECOGNITION
 PRRs-Pattern Recognition Receptors
IMMUNE CELLS
recognize
PAMPs-Pathogen
Associated
Molecular
Pattern
on PATHOGEN

7. TLR
 TLR- Type 1transmembrane receptors
 TLR3,TLR 9, TLR 7, TLR 8
 SS & DS RNA viral recognition

8. PRRs recognition
(NF)-kB &
IFN regulatory factor 3/7
Signal transduction pathway
Proinflammatory response &
Antimicrobial response

9. NF-kB
 NF-kB =Nuclear factor kappa light
chain enhancer of
activated B-cell
 Transcription factor
 cytokine production & cell survival
 Improper function cancer, viral
infection,etc.,
 NF-kB cytokine, chemokine,
IL-1, IL-18

11. IFN-1
 Type 1 Interferons are group of
interferon proteins
 Act against viral infection
 Functions:
Inhibit hiv replication
Decrease hiv infection in macrophage
RNA degradation
Viral infected cell apoptosis
• INF pDS killer pDS
infected cells killed

12. Cells involved

13. Role of Dendritic cells
• Dendritic cells- antigen presenting cells
that activates the T-lympocytes
produce INF-1
indoleamin(2,3)dioxygenase
tryptophan catabolism
viral replication inhibited

14.  Produce inflammatory cytokine & lyse
the infected cells
 Activation receptor:
KIR3DS1,NCRs, NKG 2D
 Recognize MHC-1
 Kills the infected cells
 cDCs IL-12,18 NK cell IFN γ TH1
NK cell DCs CTL response
Role of Natural Killer cells

15. Role of Macrophage
 Terminal differentiated, non dividing
cells
 Derived from circulating monocyte
Macrophage
MHC-11 MHC-1
T-helper cell Tc cells
activated activated

16.  Produce IL-10, IL-27, TGF-beta,
MCSF
 Monocyte to Macrophage
differantiation
 IL-27
 anti HIV

17. Role of Complement system
 First-line defender against foreign
pathogens
 Classical pathway involved
antibody to envelope
C1q activation
• No Alternative pathway

18. what about lectin pathway??
 Lectin pathway occur
 Need Mannose Binding Lectin(MBL)
for recognition
 But, there is no MBL on HIV.
 Then, HOW LECTIN PAHWAY occur?
 Answer:
 Serum MBL binds on gp120, activates
the lectin pathway

19. Role of Granulocyte
 Basophil activated by IgE
 releases IL-2 Th2 response occur
 Neutrophil express (PD-L1)
 Tcell affected negative regulation
 Eosinophil
 Eosinophilia occur in HIV patients =?
 during HIV Th1 response shifted to
Th2 response by IL-4, IL-5. so,
Eosinophil count increases

20. ADAPTIVE IMMUNITY
 Host defenses that are mediated by B
cells and T cells following exposure
to antigen and that exhibit specificity,
diversity, memory, and self-non self
discrimination
 3 responses involved:
 Neutralizing antibody
 T-Helper cell response
 CTL response

21. Neutralizing Antibodies
 Antibodies that bind to pathogen and
prevent it from infecting cells
 Block entry of toxin into cell
 Target the gp 120 of the HIV
viral transmission stopped
 It block transmission of HIV into fetus
 Makes HIV as LTNPs- Long Term Non
Progressor

23. Question
 HIV changes it’s structure by changing
conformation of gp120, glycosylation
of envelope protein.
 If HIV changes it’s structure, how does
the ELISA identification possible???
 Answer:
 Non Neutralizing antibodies also
produced,. It used in ELISA detection

24. T helper cell response
 T helper cells are type T lymphocytes
which recognize MHC11
 Produce cytokine that activate
immune cells
 Release IL-2, IL-4, IL-5, IL-10, IL-12,
IL-13, TNF –γ
 It responsible for the inflammation &
blocking of HIV replication

25. Cytotoxic T lymphocyte
 Recognize MHC-1 and lyse the
infected cells
 HIV infected cell
MHC-1 Expression
cell lysed

26. Mucosal Immunity

27. Mucosal….
 is a lining of mostly endodermal origin. It
consists epithelium , lamina propria
 The membranes line present in skin: at
the nostrils, the lips of the mouth,
the eyelids, the ears the genital area,
and the anus.
 In the female, the glans clitoridis and
the clitoral hood, and in the male,
the glans penis (the head of the penis)
and the inner layer of the foreskin all
have a mucous membrane.

28. Mucosal Immunity: Innate
level
 Epithelial cells & neutrophils produce
antimicrobial peptides
 Lysozyme, lactoferin, defensin
 disturb
receptors of hiv binding
cells
HIV entry
HIV-1 repelled blocked

29. Mucosal Immunity : Adaptive
level
 DCs 1st infected by HIV
bind to DC-SIGN
move to
Lymph node infected cell killed
 Vagina & cervix CD4+,CD8+ cells
destroy infected cell

30. Why there is no cure for HIV?
 It targets T lymphocytes. So all the
immune activation stopped.
 If immune activated, it will kills the T
cells, due to of HIV in it.
 Main hero's of immune cells as
MACROPHAGE, WBCs get infected
 No immunological Memory formed.
 HIV changes it’s structure.