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3rd Year Medicine


2nd Semester
2007-2008

IMMUNOLOGY
IMMUNITY TO INFECTIONS

Done by:
Sayed Ja'far Al-Salman
Al & Ahmad Al--Hiji
Computarized by:
Sayed Hasan Al-Awami

Revised by :
Zahraa AlMasery
Immunity to Infections
It is divided to 3 main groups:
1:immunity to bacteria.
2:immunity to viruses.
3:immunity to parasite.
and the immunity to fungi is digested in the middle

Immunity to bacteria
(I) Extracellular bacteria:
Most of the bacteria are extacellular. e.g Staphylococcus aureus,
strept.cooci but TB and brucella are not.
• These are usually killed by phagocytosis (either directly or indirectly but
mainly it is indirectly) and complement ( killing by Ab . Ab needs phagocytes
& complement ) , so they avoid the immune system by:

a. Avoiding phagocytosis: this is by:


(1) Having a capsule: which does not adhere to phagocytes (cover bacterial
CHO).
(2) Having anti-phagocytic surface molecules.
(and by this we mean that there are certin molcules like fimbria and other
surface molcules which will not allow the phagocytosis to be completed )
- Ab neutralize the bacterial toxins but the actual killing is done by phagocyte
and complement
(3) Secreting poisonous compounds that kill WBC.
(neutrophil is the prominant WBC and it has a role in phagocytosis )
(4) Hiding inside other cells ( !on phagocytic cells ) to avoid phagocytosis.
- Receptors on phagocytes : Toll like , lectin receptor , mannan and sugar
receptors
- The Hiding is temporarily (when attacked by phagocytes).
b. Challenging complement:
(1) Poor activation: Bacterial capsules are poor activators of alternate
complement pathway.
(2) Acceleration of complement breakdown: By binding to factor H (it
(i is part
of alternative pathway)
pathway) or cleaving factor I or by breaking C5a.
(3) Complement deviation: by secreting decoy ‫ خدعة‬proteins which keep the
complement busy. (instead
( of attacking the bacteria itself )
(4) Resistance to insertion of MAC: peptidoglycan of gram +ve organisms.

c. Antigenic variation.
- Rare ; but common in viruses & some parasites.
parasites
- Bacteria causing relapsing fever.
fever
This is a very important slide.

prevent opso nization.

C5b-C9

Prevent binding of MAC to


Membrane & prevent lysis
Host counter attack for extracellular bacteria:
bacteria

 This is based on the specificity and variability of the antibody molecule and is
done by:
(1) Toxin neutralization: antibodies neutralize soluble antiphagocytic
molecules and exotoxins e.g. phospholipase C of Clostridium Welchii.
Welchii
(2) Opsonization of bacteria: antibodies opsonize even capsulated bacteria.
This is augmented by complement
(3) Secratory immune system protects mucosal surfaces by IgA and IgM.
IgA is found in the seromucous secretion.
(4) IgE and ADCC are also present:
IgE: Activation of : Mast cell , basophiles , eosinophils & granules which
lead to destruction of the pathogen.
pathoge
ADCC: Ab & !K cell against virus & certain bacteria ( intracellular
intracellu )
Phagocytosis
with no Ab or
complement
Examples of extracellular bacteria:
 Streptococcus pyogenes (group A): (pyogenic, toxigenic complications)
- The M protein inhibits activation of complement by binding to factor H. It
also inhibits opsonization. They elicit autoantibodies.
- Exotoxins helps the bacteria and damage the host (e.g. SO, SPE A-C).
- Antibodies neutralize the bacterial toxins.

 Staphylococcus aureus:
- They resist phagocytosis by forming a capsule in vivo and by the
coagulase.
- Protein A binds to IgG and inhibit phagocytosis.
- It is capsular in vitro

(just remember that the both examples are Gm +ve)

(II) Intracellular bacteria:


 TB and leprosy bacilli, Listeria and Brucella (Listriosis & Brucellosis) live
inside the macrophages. Opsonization is normal but the intracellular killing is
inhibited because they may:
(1) Inhibit lysozymes fusing with the phagosome.
(2) Inhibit priming and activation of macrophages.
(3) Resist oxidative and lysosomal attack.
(4) Escape from phagosomes.
 Cell mediated immunity is required for defense against intracellular bacteria.
This is achieved by IF!-γ which activates macrophages leading to increase in
oxygen intermediates and NO.
Mechanism of killing intracellular bacteria ?
 Cell – mediated immunity by IFNg which activate macrophages

This table is not required


1. Binding to surface receptor on cell
2. Release its outer protein + genome
3. Replicate
IMMUNITY TO VIRUSES
Viruses evade immunity by:

(1) Antigenic variation: Some viruses change the structure of their surface
antigens.
- For example, the influenza virus changes the surface haemagglutinin (H5N1
= AVIAN INFLUINZA) the antigen which induces protective immunity.
- The change my be minor antigenic variation due to point mutation (drift) or
major due to major changes in the viral genome (shift).

(2) Antagonistic T cell epitopes: Hepatitis B virus has antagonistic epitopes


that inhibit Tc cells.

-( Inhibit Tc & activate Ts )


- !ormal T cell activation is TCR interacting with MHC loaded with an
epitope ; Viruses can displace the epitope preventing activation which may
result in chronic hepatitis .
-For activation of T cell you need antigen presentation and antigen
prossceing

(3) Affecting antigen processing and presentation:


- Adinovirus and herpes simplex virus affect processing and EBV affects
presentation.

(4) Interference with complement:


-Vaccinia virus blocks complement functions by producing product similar to
C4b binding protein .Herpes simplex destroys C3bBb convertase. Some
viruses block complement binding to their receptors (EBV). HIV, when
opsonized with complement and antibodies becomes more virulent.
- ( Complement attack viruses when they are outside the cell )

(5) Interference with cell mediated immunity:


- Parainfluenza viruses inhibit Tc cells. EBV inhibits IFN-γ.
- HIV is one step ahead for the other viruses bcz the other viruses try to
block the effect of complement and Ab while HIV is using them to enter
the cells
Host responses to viruses:
viruses
(1) Local factors: This is part of the innate immunity. It is important in
influenza. The most significant are the interferons.
(2) Antibodies: Antibodies can interfere with virus entry to cell or spread
from one cell to another. Antibodies can destroy free viruses through
activation of classical complement pathway or through enhancement of
phagocytosis. Antibodies in mucosal surfaces in secretions secretion prevent
subsequent infection.
- Antibodies play an important role in preventing re-infection
re infection with most
viruses.
(3) Cell mediated immunity (CMI): CMI is important for fight against
viruses. First line of defense is NK cells that kill virally infected cells.
cel Tc kills
virally infected cells when the TCR recognizes MHC class 1 and antigens.
TH cells are needed in certain infections.
(4) Cytokines:: Secreted by Tc and TH cells and by phagocytes. They bring
WBC to the infected area and they protect cells from infection with viruses.
(5) ADCC:: Done by NK cells. Important in measles etc.
1. Viremia
2. !k ( innate )
3. CTL
4. Ab
IMMUNITY TO FUNGI
 Many fungal infections occur in patients with depressed immunity or patients
with long periods of antibiotics.
 T cells are important in defense (Cryptococcus neoformans and Candida
albicans).
 NK cells also lyse c.neoformans.
 ( Immunity to fungi is cell mediated

IMMUNITY TO PARASITES
- There are more than 100 millions people infected with malaria or
schistosoma or hookworms.

Host responses:
- In general, humoral responses develop when the parasites invade the blood
stream (malaria, trypanosoma). Parasites which grow within tissues (e.g.
cutaneous lishmaniasis) usually induce cell-mediated immunity.
- Infection with one parasite may make the host resistant to infection with
fresh organism (e.g. malaria and schistosoma).
- There is no one single vaccine for any parasite
- Humoral immunity is important for blood parasites
- Cell-mediated immunity is important for tissue parasites
 Humoral immunity to parasites:
Antibodies protect against blood born parasites such as trypanosoma brucei
and malaria. This is done by opsonization (phagocytosis) and complement
activation (lysis).
- In helminthic infections the patients have high levels of IgE and high
eosinophils counts.
- IgE release mast cells mediators which lead to chemotaxis of WBC and
serum proteins.
- IgE and IgG bind to parasites on one end and to eosinophils on the other
side. This leads to extracellular killing.
- IgE is important for recovery from parasitic infections and IgG and IgA
are important for vaccination.
- CMI to parasites: Like mycobacteria, intracellular parasites such as
Toxoplasma, Trypanosoma and Leishmania live inside macrophages.

- T cells secreting IF-γ and TF-α stimulate macrophages to kill the


intracellular parasites (NO).
- TH1 (Cytokines) and Tc (Cytokine and direct killing) are important in
protection.
 Humoral immunity :
- IgE ( Mast cells , basophiles , eosinophils )
- IgG ( only Eosinophils )
- Opsonization & phagocytosis is for protozoa
( i.e. they are small )

THIS IS A VERY IMPORTANT DIAGRAM…..


DIAGRAM
Evasion strategies by parasites:

(A) Resistant to effector mechanisms:

(1) Secretion of DAF-like molecules that destroy C3b.


1 accelerate the break down
2 Prevent C4 & C5a – 8 to attach
(2) Ejection of bound C3 antibody.
( prevent attachment of C3 to Ab )
(3) Secretion of decoy proteins. ( keep the complement busy )
(4) Hiding inside other cells.
(5) Blocking normal killing mechanisms of phagocytes by blocking
phagolysosomal fusion or by escaping into the cytoplasm. They also down
regulate MHC and B7 expression.

(B) Avoiding antigen recognition by the host:


(1) Some parasites disguise themselves to look like host by molecular mimicry
(Ascaris antigens look like human collagen) or by covering the surface with
host proteins.
(2) Antigenic variation: to escape from antibodies e.g. Trypanosoma (
equivelunt to influnza virus ). When the host develop specific antibodies the
parasite switch new antigenic variant. The parasite stays long enough to
allow transmission to other host.
(3) Deviation of the host immune response:
- In some parasitic infections, the antibodies and CMI are 10% of normal.
Some parasites inhibit IgE or TH2 or ADCC responses.