Immunity to infections. Prof. Mohamed Osman Gad El Rab. College of Medicine& KKUH.

Classification of immunity. classification of acquired immunity. active. passive. natural. artificial. infections. immuniz. Maternal immuno - IgG. therapy. Subclinical. Clinical. Vaccines. IgG from mother to fetus. Ready made antibodies. generated outside the body, NOT from the immune system type of immunity generated by the immune system

General features : First encounter with any microbe (at any age) : * Lead to Primary immune response. * which include 4 phases : 1. lag (preparation) (no antibodies) 2. log. (antibodies appear ) 3. plateau.( no more synthesis ) 4. decline.( antibody disappear ). (decline Is fast compared to 2ry response)

lag log plateau decline phases Antibody level

Primary immune response : 1. takes a longer time ( recognition of antigen, differentiation & proliferation of cells ). 2. antibody class present is mainly IgM. IgM is the first to be produced in primary response 3. memory cells generated.

Second encounter with same microbe : Secondary immune response : 1.require small amount of antigen. 2. fast reaction ( memory cells ). 3. high levels of antibody ( IgG ). IgG appears in 2ry exposure General features :

Nature of infecting microbe determine type of response. extracellular microbes. ( bacteria) Th 2 helper cells. antibody- mediated immunity.

intracellular microbes. ( viruses, intracellular bacteria, fungi ) Th 1 helper cells. cell- mediated immunity.

Th1, Th2 cells down-regulate each other. 1. each cell type secrete different cytokines. 2. balance between Th1 & Th2 determine the clinical presentation of the disease.

The balance between TH1 & TH2 is important in immunity. It determine the clinical presentation of the disease. Macrophages (Antigen Presenting Cell) T H cell

Many factors influence immune response to infections: 1. structure of the microbe antigen : How strongly the antigen stimulates a response (depends on some specific amino acid sequences) Strong antigen  induce immune system more, weak antigen  takes more time to induce immune system (e.g. HIV) 2. dose of infection ( optimum dose, good response) 3. route of entry into the tissues ( determine site of reaction) To reduce the effect of an antigen which affects a specific site, cover the site of entry leading to that site. e.g. if an antigen affects the lung, to protect against this antigen expose the nasal airway less. 4. host factors : - genetic constitution - age

Immunity to bacterial infections : extracellular intracellular protection by antibody-mediated cell-mediated immunity immunity

Adherence

Penetration into the host Cell Figure 15.2 Salmonella entering epithelial cells via invasins

protective functions of antibodies : 1. neutralizing action (mediated by antibodies) : - prevent pathogens from binding to tissues -prevent the action of toxins -So (covers the receptors on the toxin or virus) 2. activate complement 3. stimulate phagocytosis 4. stimulate NK-cell-mediated killing 2,3,4 activated by ( antibody-antigen reaction )

Protective functions of antibodies.

microbial strategies to avoid the immune system : e.g. Pneumococcus has large polysaccharide coat طاقية الاخفاء ^_^ not recognised by immune system * can evade phagocytosis Mycobacteria have waxy coat & secrete catalase * can block respiratory burst by catalase

In chronic intracellular infections e.g. T.B. excessive CMI responses lead to granuloma formation

Granuloma formation ( T.B. )

Complications of immune responses In some cases, disease is not caused by the bacteria but rather by the immune response So the complications and the problems in the disease are caused by the immune system 

1.Endotoxins of gram –ve bacteria (lipopolysaccharides) activate macrophages which release high levels of IL-1, & TNF - alpha, these may cause : Septic shock (due to septicemia, infection in blood) Treatment: anti-TNF, anti-IL1 Examples

2.In staphylococcal ( food – poisoning ), enterotoxins ( a protein toxin released by a microorganism in the intestine ) act as superantigens and cause direct massive T-cell activation This may cause : ] Toxic shock syndrome[ Superantigens activate T-cells directly, without the need of APC for activation

NOTE Septic shock is caused by septicemia, which is a state of high bacteria in blood. So bacteria is the direct cause of septic shock. Toxic shock syndrome is caused by toxins

immunity to viral infections : Initially : 1. Interferon, secreted by : - infected cells (macrophages) - inflammatory cells (T lymphocytes) can : 1- directly kill viruses 2- makes cell wall of our body resistant to viruses 2. NK- cells

Antibody- mediated immunity : Anti-viral antibodies : 1. Prevent spread during acute infection (or vaccination) 2. Protect against re-infection

adaptive immune mechanisms : Cell-mediated immunity * activation of CD8 T-cells. - inhibit viral replication. - kill infected cells.

Viruses can evade host defenses. 1. Hepatitis C virus : overcome (anti – viral) effect of INFs by blocking the action of protein kinase Protein kinase is a metabolic pathway for killing viruses inside cells 2. Adenoviruses & CMV ( a type of Herpes virus ) : reduce surface expression of MHC-1

Influenza virus

1. Antigenic drift: (random mutations in genes) gradual minor change in HA & NA small changes in the genes of one DNA stretch of one virus to evade the immune system 2. Antigenic shift: (re assortment or mixing of genetic material) sudden major change in HA & NA ( new subtypes emerge ) Fusion between 2 DNA stretches from more than one virus that change the virus into a new form So a strange DNA is inserted into the virus to form a new set of DNA, so a new virus is formed

Immunity to parasitic infections:

The type of the immune response depend on the location of the parasite in the host In the blood antibodies may be effective in the intracellular stage CMI may be effective

Immunity to Malaria: Caused by genus Plasmodium. P. falciparum is the most virulent & prevalent Infect 10% of the population. Causes 1– 2 million deaths every year Have a complex life – cycle (many antigens appear during infection) Vaccines are difficult for malaria, because it changes its antigens in each stage

Life cycle of malaria : 3-stages.

During the life- cycle, many antigens appear : Infection begin with mosquito bite Sporozoites enter the blood & disappear within 30 min * Migrate to the liver & after one week release merozoites which infect RBCs

Sporozoites stay for only 30 min. in the blood, therefore induce a poor immune response The intracellular stage in the liver cells and RBC, reduce the degree of immune activation generated by the pathogen (note that RBC does not have MHC)

So, in case of malaria there is poor immune response because : 1- the Sporozoites stay in blood for short time ( 30 min ) to induce immune response 2- RBC’s does not have MHC, so there is no presentation

Immunity to parasitic worms (helminthes): Helminthes are large multicellular organisms e.g. Schistosoma (Bilharzia) Have complex life- cycle

Cercaria enter the blood stream and become schistosomules which enter capilleries then pass to the lungs & liver and become adult worms

Humoral immune responses to parasites are characterized by : 1. Elevated IgE 2. Blood eosinophilia Eosinophils mediate ADCC (antibody directed cellular cytotoxicity) to damage the parasite