Immunology.docx

Immunology Body defense may be:-

Non-specific resistance

specific resistance

1st line

2nd line

3rd line of defense

Skin & mucos

. Phagocytosis

Membrane

B, T lymphocytes

. Inflammation & fever

antibodies.

- Phagocytes are neutrophiles & monocytes. - Chemotaxis is the chemical attraction of phagocytes towards the site of infection through chemotactic factors. - Infection increase the number of leukocytes "leukocytosis" - Fever is the systemic response of the body to infection or injury. - The complement system:- is a group of 20 or more proteins present in blood. - Complement system increase the action of antibodies in killing microorganism. - Classical pathway activation of complement :- Ag-Ab complex activate C1 - Alternative pathway activation of complement :Activation doesn't involve Abs but occur through polysaccharides. - The complement system remove Ag – Ab complex from the circulation as if Ag – Ab complex ppt in the kidney it will cause glomeruloneohritis. - C-reactivate protein "C-RP" :- it is one of the acute phase proteins, synthetized in liver, can activate complement system so kill m.o. .it's a marker of inflammation. And reach its peak after 24 hour. - Antistreptolysino "ASO": It is antibody produce by the body as defense mech. against streptolysin which is an enzyme produced by the invading streptococci.

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:. ASO in case of streptococci & if untreated Aso react W the heart muscle tissue causing "rheumatic fever" - Interferon α, B, Ϫ α,B produced from the infected cells. Ϫ produced from T-lymphocytes. .IFN has an antiviral activity. .IFN is host cell specific but not virus specific as human IFN has only activity in human but against all viruses. When the cell is infected with a virus, the cell process the virus into small protein fragments that move to the surface of the infected cell acting as antigens these antigens are present in association with MHC which act as presenters for those antigens so these antigens are well marked and highly lighted for t-cells. . ͘ . MHC major histocom patibility cpx ‫ ) لكى تتعرف عليها ونقوم بقتلها‬Tc( ‫) ل‬viral parts)‫و هى تعمل مثل الصينيه لتقديم ال‬

Immunity Naturally acquired

artificially acquired

Active passive Ag enter the readymade Abs pass Blood so freely from the mother Body from Ab. To the baby during Pregnancy or during Colostrums "lactation"

active passive pathogen is given in ready made Ab injection e.g. vaccine e.g. serum

Serology is the study of reactions between Ags and Abs. Abs separated from serum by Gel-electrophores is Antibody ≡ Ϫ globulin ≡ Immunoglobulin ≡ Ig.

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Antigen "Ag": material that induces production of antibodies when injected Into the body. Has large M.WT ≥ 10,000 Dalton. Mainly proteins or large Polysaccharides . Ag may be the whole bacterial cell, capsule, flagella, viral coats, Toxins, pollen grains, dust or egg white. Epitopes is a specific regions on Ags which the Ab recognize it and bind to it. Haptens: - foreign substance having low M.WT it's not immunogenic, Can't stimulate the immune system to produce Abs. Hapten + carrier

Ag "immunogenic"

Example of haptens is penicillin. Antibodies"Abs" are proteins made in respone to antigen And it can recognize it and bind with it. Most of Abs are bivalent "have 2 antigen binding site" Ab structures

4 protein chains

2 light "L". 2 heavy "H". Intra disulfide links bet. 2H but inter sulfide bond bet bet. H and L. Ab has a Y shape and the lower parts of the Y shape is the constant Region "C" Fc region

composed of the 2 heavy chains "The lower part".

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The end of the two arms of the Y-shape are called variable Region "V" which is the antigen binding sites. The real form of Ab is the Y-shape structure in which the amino acid Forming the chains exist in form of domains. L has 2 domains VL and CL H has 4 domains VH and 3 CH Constant region of heavy chain has many different amino acid sequences resulting in 5 different classes of Ig (s). IgA, IgG, IgE, IgM, IgD. IgM is the first Ab secreted due to initial infection.

I9G structure

monomer

I9M

I9A

pentamer

Diamer

I9D monomer

I9E monomer

% of total Abs serum

80%

5-10%

5-10%

0.2%

0.002%

Complement fixation Placental transfer

yes

yes

No

No

No

Yes

No

No

No

No

location

function

Blood, lymph, and intestine

Blood, Secretions lymph, B-cell "salvia, mucus, surfaces milk, blood, lymph" phagocytosis 1 ˢᵗ Ig Protection on secreted mucosal surface

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B-cell surface

Bound to mast cell

Immune responce

Allergic Rx.

Humoral immunity (Ab –mediated immunity) :Through circulating Abs W are secreted from B-cells. B-cells activation activated B-cells differentiated into plasma cells Specific Ab produce + Memory cells

Cell-mediated immunity: - depend on t-cells And act against pathogen intracellular not Circulating. And fight cancer cells.

Stem cells Produce

present in bone Marrow in adult and In liver of foetus.

Immature

immature

B-cells

T-cells

Maturation

maturation

In bone marrow

in thymus gland

Mature B-cell

mature t-cell.

Activation by Ag(s) on pathogen

Activated B-cells

activated

Differentiation

cytotoxic (tc)

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Plasma cells +memory cell form

attack cancer cells and

Ab(s) specific for

intracellular ,

The Ag

viruses , Bacteria.

Every single B-cell can be activated only by one specific Ag "Key and lock". Each B-cell can bind only to one Ag using the Ag Receptor (Igd, IgM) Which are bound to the surface of B-cell then the B-cell is activated. Activated B-cells

plasma cells + memory cells "Long term immunity".

The human body make 100 million lymphocytes each day so an equivalent No. of other lymphocytes must die otherwise leukemia occur. So Apoptosis

is a programmed cell death.

The 1ˢᵗ Ab formed IgM followed by IgG. Experianent in rabbit. B-cells

cancerous B-cell

cant produces Abs but contine

"Myelomas"

Hybrid cell

In

in grouth in cultne.

B-cells + myeloma fusion

selective medium

hybridoma

Produce monoclonal Ab.

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Cytokines is the chemical messengers of immune cells. Interleukins are cytokines that serve as chemical messenger between leuckocytes.

The cells that introduce the Ag on its surface are called "antigen presenting cells"APC(s)". CD4 types:- TH and TD. Types of t-cells CD8 types: - Tc and Ts. TH "helper": - activate the cytotoxic T cells Activate the macrophage Help B-cells to produce Ab(s).

TD "delay hypersensitivity t cells": Involve in allergic reaction Involve in rejection of transplanted tissue. Fight intracellular Ag.

Tc "cytotoxic": - attack infected host cells and Destroy them by secreting perforins and Lytic enzymes.

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Ts "suppressor": - regulate the immune response by turning it off when Ag is no longer present.

TC bind to MHC-antigen cpx on infested cell surface, Tc release perforins W lyse cell.

Vaccines: 1-Live attenuated: - make the organism immunogenic but not pathogenic E.g. Sabine vaccine. 2-Killed: - the organism is killed by formalin or phenol E.g. Rabies vaccine, salk vaccines and cholera, influenza. 3-Toxoid: -toxin inactivated toxoid E.g. tetanus and Diphtheria. 4- Subunit vaccine "recombinant vaccine". E.g. hepatitis B.

Hypersensitivity Rx: -

Anaphylactic

cytotoxic

Type 1

type 2

immune cpx type 3

cell-modiated or delay type Type 4

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1-type 1 "anaphylactic" IgE produced on the 1ˢᵗ exposure to the allergen and attach to mast cells or basophiles so on the 2ⁿᵈ Exposure mast cell degradation and releasing of histamine and leukotrienes and vasodilatation, mucous secretion B.V permeability and bronchoconstriction. E.g. pollen grains, eating fish, nuts, strawberry, Hay fever, urtecaria, asthma. In non-allergic people, igG produced.

2- Type TT "cytotoxic": involve the activation of the complement. E.g. blood transfusion, Type O

lack A and B Ag(s),

Type AB

has A and B Ag (s),but lack Ab(s) to them.

Blood type O is universal donor. And blood type AB is universal recipient. RH factor: Father+Rh Child +RH mother-ve RH

RBCs of child + Ve through to the placenta

mother –Rh IgG

2ⁿᵈ pregncy

IgG

Pass to the +ve RH child

"antiRh" hemolytic disease of newborn.

3- Type 3 which is Drug hypersensitivity. 4- Type 4 : cell mediated Rx "delayed type" TD cells are involved.

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E.g. allergic contact dermatitis soap,Gloves "latex one" Poison ivy. And tuberculin Rx by mycobacterial Ag

Autoimmune disease the production of Ab(s) against the persons own tissue Ag(s).

1-Graves disease: due to Ab(s) called long acting thyroid stimulators. "TSH receptor" Ab binds to receptors on thyroid gland so thyroid hormones amount so hyperthyroidism.

2- Myasthenia gravis: gradual loss of muscular tone caused by the Ab(s) that Coat the Ach receptor at the NMJ "neuromuscular junction". So the muscle controlling the diaphragm don’t receive the Nerve signals Respiratory death. 3- Pernicious anemia: - vit B₁₂ need intrinsic factor to be absorber And her there are Ab(s) to the intrinsic factor so vit B₁₂ can't bind to the Intrinsic factor so Vit B₁₂ deficiency. 4- Rheumatoid arthritis: - immune cpx of IgM and IgG are deposited in joints affect females> male. 5- Systemic lupus erythromatous (SLE): Ab(s) against DNA are formed . ͘ . Ab-self AgDNA cpx

deposit in much tissue causing glomerulonephritis.

6- hashimotoo thyroditis : T-cell attack thyroid gland cell and causing hypothyroidism.

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7- IDDM

t-cell attack and destroy B-cell of lengerhans.

8- Good pasture syndrome: Abs against capillary absement membrane (GMB) . ͘ . nephritis and these Abs may pass to the Pulmonary capillary basement membrane causing Pulmonary hemorrhage. 9-Multiple sclerosis (MS): T-cell attack the basic protein myelin Leading to CNS demylination with sclerotic plaque. 10-sojorin syndrome: Abs against salivary gland antigens and exocrine glands of the eye, GIT and RT and vagina so no exocrine gland secretion.

Autoimmune diseases

Type 2 Autoimmune

type 3

type 4

autoimmune

hashimotos

Disease

disease

thyroditis

Pernicious Anemia

SLE

IDDM

Graves's disease

Rheumatoid

Myasthenia gravis.

Arthritis

Tolerogens cpds are broken by the body and have specific no responsiveness.

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TTT of type 1 hypersensitivity reaction: 1-H₁ blocker. 2-EPi. 3-cromolyn Na⁺. 4-topical steroids.

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