Check out how alcohol degrades immune system and its components.

1. EFFECTS OF ALCOHOLISM ON
IMMUNE RESPONSE

2. PATHOGEN & MOLECULAR
REGULATION
• Whenever the human body encounters a foreign
particle, the immunological response is triggered in
the following manner,
Firstly, the antigen binds to the cell
surface receptor.
The receptor then conveys a signal to
the cell’s interior & then to the nucleus.
Then the cellular DNA directs the
synthesis of proteins specific to the
antigen.

3. ALCOHOLISM vs MOLECULAR
REGULATION
• Alcohol alters the molecular mechanisms that
control cellular responses to normal stimuli.
• There are no specific receptors for alcohol.
• Alcohol disturbs the normal molecular regulation in
two ways,
Modifies the structure of the receptors
harbored in the cell.
By frequently fluctuating the ionic
concentration (K⁺, Ca⁺⁺) in the cell.

4. • Both potassium and calcium ion concentrations
change rapidly in the cell’s interior during various
types of cell activation events.
• They act as indirect indicators of changes within the
cell.
IONIC BALANCE

5. IONIC FLUCTUATIONS
• After short-term alcohol exposure, potassium
conductance increases(potassium channels in the
cell membrane are opened) in T-cells.
• Intracellular calcium concentrations are shifted in
neutrophils and in Kupffer cells.

6. EFFECT OF ALCOHOLISM – A CASE OF
kappa B (NFκB).
• One of the cytoplasmic elements involved in the
activation of cellular responses is a transcription
factor called nuclear factor kappa B (NFκB).
• This molecular complex is activated by signaling
events.
• It is then transported to the nucleus, where it binds
to DNA and initiates the synthesis of mRNA.

7. • The study of human cells reported that alcohol
disturbs the NFκB complex in such a way that the
signal to the nucleus is inhibitory rather than
stimulatory.

8. EFFECTS AT MACRO LEVEL
• Alcohol has a great array of effects at the cellular and
organ levels.
• The primerily targeted organ is Liver.
• Alcohols greatly increase the level of undesired
immunoglobulins in blood.
• The major classes of these antibodies are
immunoglobulins A, G, and M ( IgA, IgG, and
IgM), each of which has a specialized role in the
immune response.

9. ELEVATION OF ANTIBODIES
• Typically, IgA is elevated in the blood of alcoholics
both with and without alcoholic liver disease.
• IgG is elevated in those with liver disease.
• IgM is also elevated only in patients with active liver
disease, such as alcoholic hepatitis.
• IgA also may be found as tissue deposits in the
skin, liver and kidney of alcoholics.

10. AUTOIMMUNITY
• These higher antibody levels may be due to
abnormal regulation in the production of
antibodies, or they might be a manifestation of
autoimmunity.
• Most of the antibody produced attack the self-
cells.(Autoimmune in nature)
• Alcohol-triggered autoimmunity.

11. ALCOHOLISM
• Alcoholics without liver disease typically have normal
number of lymphocytes in their peripheral
blood, while those with liver disease have a wide
range of abnormalities.
• In patients with alcoholic hepatitis (an earlier stage
of alcoholic liver disease), there is a mild reduction in
lymphocyte numbers, with a return to normal levels
after several weeks of recovery.

12. • Patients with alcoholic cirrhosis (a later stage of
alcoholic liver disease) may have lymphopenia, a
severe reduction in lymphocyte numbers.
• Abnormalities of immune function can be
accompanied by changes in the percentages of
different types or subsets of lymphocytes.
• Changes in cell surface markers might also occur.

13. NUTROPHILS
• In alcoholic hepatitis, there is an increase in the
number of neutrophils in the blood.
• Since these cells typically release powerful enzymes
that damage tissue, an abnormal number of
neutrophils in the liver of alcoholics is one possible
mechanism for liver damage.

14. T-CELLS & B-CELLS
• In patients with alcoholic liver disease, the ratio of
helper T-cells (designated CD4) to cytotoxic and
suppressor T-cells (designated CD8) is abnormal.
• In patients with alcoholic liver disease, B-cells are
often decreased in number.

15. • Cytokine balance is disrupted in alcoholic liver
disease.
• The monocytes in the bloodstream and the
macrophages such as the Kupffer cells in the liver
produce an excess of the proinflammatory cytokines
IL-1, IL-6, and TNF in response to alcohol.

16. MONOCYTE AND MACROPHAGE-DERIVED
SUBSTANCES POTENTIALLY AFFECTED BY
ALCOHOL

17. • These same cells are sensitive to stimulation by a
lipopolysaccharide, known as LPS or endotoxin, a
toxic substance produced in the cell walls of bacteria
that commonly reside in the intestine.
• LPS is a powerful activator of many immune system
cells.
• It can potentiate the effects of alcohol in activating
macrophages, particularly the Kupffer cells.

18. ROS
• Cells of the innate immune system produce reactive
oxygen species (ROS), toxic substances that kill
bacteria and causes inflammation.
• Studies of liver injury find that alcohol-fed animals
have higher levels of ROS resulting from increased
NO(nitric oxide) production.

19. ACETALDEHYDE-PROTEIN ADDUCTS
• Acetaldehyde, the first product of alcohol
metabolism is reactive and combines chemically
with proteins in the cells or blood of the person
consuming the alcohol.
• These chemical combinations are called adducts.
• The development of autoimmunity after alcohol
exposure may be a result of the formation of
these acetaldehyde-protein adducts.

20. • Alcoholics show increased susceptibility to,
Pneumonia (MacGregor and
Louria1997)
Tuberculosis(Centers for Disease
Control and Prevention[CDC] 1996)
HIV - AIDS (MacGregor and
Louria1997)
Cancer(Centers for Disease Control
and Prevention[CDC] 1996)

21. REFERENCES
• Zhang, P.; Nelson, S.; Summer, W.R.; and Spitzer, J.A.
Acute ethanol intoxication suppresses the pulmonary
inflammatory response in rats challenged with
intrapulmonary endotoxin. Alcohol Clin Exp Res
21(5):773–778, 1997b.
• Zeldin, G.; Yang, S.Q.; Yin, M.; Lin, H.Z.;Rai, R.; and
Diehl, A.M. Alcohol and cytokineinducible
transcription factors [Review]. Alcohol Clin Exp Res
20(9):1639–1645, 1996.

22. • Viitala, K.; Israel, Y.; Blake, J.E.; and Niemela, O.
Serum IgA, IgG, and IgM antibodies directed against
acetaldehyde-derived epitopes: Relationship to liver
disease severity and alcohol consumption.
Hepatology 25(6):1418–1424, 1997.
• LE Dı´az, A Montero, M Gonza´lez-Gross, AI Vallejo, J
Romeo and A Marcos Influence of alcohol
consumption on immunological status: a review
European Journal of Clinical Nutrition (2002)
56, Suppl 3, S50–S53 2002 Nature Publishing Group

23. Spread awareness about the ill-
effects
of ALCOHOLISM, NOT THE HABIT
- anonymous